Aromatic carboxylic acids in combination with aromatic hydroxyamides for  inactivating non-enveloped viruses

ABSTRACT

The present invention is directed to antiviral compositions that provide efficacy against non-envelope viruses such as noroviruses. The antiviral compositions comprise an alcohol and a synergistic combination of an aromatic carboxylic acid and an aromatic hydroxyamide. The composition may be used as a topical on human skin, as a hand sanitizer or as a hard surface cleaning composition.

FIELD OF THE INVENTION

The present invention relates to antiviral compositions having efficacyagainst non-enveloped viruses such as norovirus. More particularly, thepresent invention relates to antimicrobial compositions for use intopical skin applications, hand sanitizer compositions, hard surfacecleaners and the like, comprising an alcohol and a synergisticcombination of aromatic carboxylic acids and an aromatic hydroxyamide.The compositions are effective at inactivating and reducing viralpopulations of non-enveloped viruses by greater than 3 logs.

BACKGROUND OF THE INVENTION

Pathogenic viruses can be classified into two general types with respectto the viral structure: enveloped viruses and non-enveloped viruses.Some well-known enveloped viruses include herpes virus, influenza virus;paramyxovirus, respiratory syncytial virus, corona virus, HIV, hepatitisB virus, hepatitis C virus and SARS-CoV virus. Non-enveloped viruses,sometimes referred to as “naked” viruses, include the familiesPicornaviridae, Reoviridae, Caliciviridae, Adenoviridae andParvoviridae. Members of these families include rhinovirus, poliovirus,adenovirus, hepatitis A virus, norovirus, papillomavirus, and rotavirus.

It is known in the art that “enveloped” viruses are relatively sensitiveand, thus, can be inactivated by commonly used disinfectants. Incontrast, non-enveloped viruses are substantially more resistant toconventional disinfectants and are significantly more environmentallystable than enveloped viruses. Although a number of non-envelopedviruses can be inactivated with relatively high concentrations offormaldehyde, the use of formaldehyde is undesirable because of itstoxicity.

The non-enveloped virus Norovirus (NoV), also known previously as“Norwalk-Like Virus” (NLV) or small round structured virus, is the mostimportant viral pathogen of epidemic acute gastroenteritis that occursin both developed and developing countries. NoV belongs to theCaliciviridae family and are icosahedral, single stranded,positive-sense RNA viruses whose capsids are composed of 180 copies of asingle major structural protein. Noroviruses are estimated to cause 23million cases of acute gastroenteritis in the United States per year,and are the leading cause of gastroenteritis in the United States. Ofviruses, only the common cold is reported more often than viralgastroenteritis (norovirus). Norovirus causes nausea, vomiting(sometimes accompanied by diarrhea), and stomach cramps. This infectiontypically is spread from person to person by direct contact.

Noroviruses are very highly contagious and can spread easily from personto person. People can become infected with the norovirus in severalways, including, eating food or drinking liquids that are contaminatedwith norovirus; touching surfaces or objects contaminated withnorovirus, and then placing their hands in their mouths; or havingdirect contact with another person who is infected and showing symptoms(for example, when caring for someone who is ill, or sharing foods oreating utensils with someone who is ill). During outbreaks of norovirusgastroenteritis, several modes of transmission have been documented, forexample, initial foodborne transmission in a restaurant, followed bysecondary person-to-person transmission to household contacts. Noevidence suggests that norovirus infection occurs through therespiratory system.

Protracted outbreaks of norovirus disease have been reported amongelderly persons living in institutional settings, e.g., nursing homes.In some cases, the outbreak was initially caused by exposure to afecally-contaminated vehicle (e.g., food or water). Then, the outbreakspreads through person-to-person transmission among the residents. Thisspread is facilitated by the enclosed living quarters and reduced levelsof personal hygiene that result from incontinence, immobility, orreduced mental alertness. Because of underlying medical conditions, thedisease among these elderly persons can be severe or fatal.

Passengers and crew members on cruise ships and naval vessels arefrequently affected by outbreaks of gastroenteritis. Cruise ships oftendock in countries where sanitation levels are inadequate, thusincreasing the contamination risk of water and food taken aboard orhaving a passenger board with an active infection. After a passenger orcrew member brings the norovirus on board, the close living quarters onships amplify opportunities for person-to-person transmission.Furthermore, the arrival of new and susceptible passengers every fewdays or weeks on affected cruise ships provides an opportunity forsustained transmission during successive cruises. Norovirus outbreaksextending beyond twelve successive cruises have been reported.

Currently, no antiviral medication against norovirus is available, andno standard method to prevent infection exists. Norovirus infectioncannot be treated with antibiotics. Noroviruses also are relativelyresistant to environmental challenge. Noroviruses can survive freezing,temperatures as high as 60° C., and even have been associated withillness after being steamed in shellfish. Moreover, noroviruses cansurvive in up to 10 ppm chlorine, which is well in excess of chlorinelevels routinely present in public water systems. Accordingly it is anobject herein to provide a composition for inactivation of non-envelopedviruses that is may be used topically on skin and can also function as ahard surface cleaner.

It is yet another object of the invention to provide a composition andmethod for viral inactivation of non-enveloped viruses that results in agreater than 3 log reduction of a population.

Other objects, aspects and advantages of this invention will be apparentto one skilled in the art in view of the following disclosure, thedrawings, and the appended claims.

SUMMARY OF THE INVENTION

The present invention is directed to antiviral compositions that providerapid antimicrobial effectiveness against noroviruses. The compositionsprovide a substantial reduction in norovirus population, up to 3 logs inless than about one minute.

More particularly, the present invention relates to antiviralcompositions comprising a synergistic combination of an alcohol, anaromatic carboxylic acid and an aromatic hydroxyamide. The compositionmay be used as a topical on human skin, as a hand sanitizer or as a hardsurface cleaning composition.

Another aspect of the present invention is to provide a liquid,antiviral composition comprising:

-   -   (a) about 30% to about 99%, by weight, of a linear and/or        branchedC₁₋₆ alcohol;    -   (b) a virucidally effective amount of an aromatic carboxylic        acid;    -   (c) a virucidally effective amount of an aromatic hydroxyamide;        and    -   (d) water;        wherein the composition has a pH of about 2.5 to about 6.8 for        topical formulations, and 1.0 to about 6.8 for a hard surface        cleaning formulation. The invention may also optionally include        a surfactant, particularly a sulfonated surfactant. Additional        functional components and excipients may also be present.

Another aspect of the present invention is to provide an antiviralcomposition having antiviral activity comprising a C1-C6 linear and/orbranched alcohol, an aromatic carboxylic acid such as salicylic acid,benzoic acid salts, and derivatives thereof; and an aromatichydroxyamide. These aromatic carboxylic acids and aromatic hydroxyamidesmay be used singly or in combination of two or more species inaccordance the invention. Among them, salicylic acids are particularlypreferred.

Another aspect of the present invention is to provide an antiviralcomposition that exhibits a log reduction against norovirus. Theantimicrobial composition also preferably provides a log reductionagainst norovirus of at least 2 for at least about four hours, and atleast 2 for at least about six hours, after application with a 30 secondcontact time. In some embodiments, the antimicrobial compositionprovides a log reduction against noroviruses of about 2 for up to abouteight hours.

A further aspect of the present invention is to provide a method ofquickly controlling norovirus populations on animal tissue, includinghuman tissue, by contacting the tissue, like the dermis, with acomposition of the present invention for a sufficient time, for example,about 15 seconds to 5 minutes or longer, e.g., about one hour, to reducebacterial and norovirus population levels to a desired level. A furtheraspect of the present invention is to provide a composition thatexhibits a persistent control of noroviruses on animal tissue.

Yet another aspect of the present invention is to provide a compositionand method of interrupting transmission of a norovirus from animate andinanimate surfaces to an animate surface, especially human skin andmouth. Especially provided is a method and composition for controllingthe transmission of norovirus by effectively controlling norovirusespresent on human skin and continuing to control noroviruses for a periodof about four or more hours, and up to about eight hours, afterapplication of the composition to the skin.

The antiviral compositions of the present invention are highlyefficacious in household cleaning applications (e.g., hard surfaces,like floors, countertops, tubs, dishes, and softer cloth materials, likeclothing), personal care applications (e.g., lotions, shower gels,soaps, shampoos, and wipes), and industrial and hospital applications(e.g., sterilization of instruments, medical devices, and gloves). Thepresent compositions efficaciously and rapidly clean and disinfectsurfaces that are infected or contaminated with non-enveloped virusessuch as norovirus. The present compositions also provide a persistentantiviral effectiveness.

Another aspect of the present invention is to provide consumer productsbased on an antiviral composition of the present invention, for example,a skin cleanser, a body splash, a surgical scrub, a wound care agent, ahand sanitizer gel, a disinfectant, a pet shampoo, a hard surfacesanitizer, a lotion, an ointment, a cream, a swab, a wipe, and the like.A composition of the present invention can be a rinse-off product, butpreferably is a leave-on product.

These and other novel aspects and advantages of the present inventionare set forth in the following, nonlimiting detailed description of thepreferred embodiments

DETAILED DESCRIPTION OF THE INVENTION

While the presently described technology will be described in connectionwith one or more preferred embodiments, it will be understood by thoseskilled in the art that the technology is not limited to only thoseparticular embodiments. To the contrary, the presently describedtechnology includes all alternatives, modifications, and equivalents asmay be included within the spirit and scope of the appended claims.

“Cleaning” means to perform or aid in soil removal, bleaching, microbialpopulation reduction, rinsing, or combination thereof.

It should be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the content clearly dictates otherwise. Thus, for example,reference to a composition containing “a compound” includes a mixture oftwo or more compounds. It should also be noted that the term “or” isgenerally employed in its sense including “and/or” unless the contentclearly dictates otherwise.

The term “actives” or “percent actives” or “percent by weight actives”or “actives concentration” are used interchangeably herein and refers tothe concentration of those ingredients involved in cleaning expressed asa percentage minus inert ingredients such as water or salts.

As used herein, “weight percent,” “wt. %,” “percent by weight,” “% byweight,” and variations thereof refer to the concentration of asubstance as the weight of that substance divided by the total weight ofthe composition and multiplied by 100. It is understood that, as usedhere, “percent,” “%,” and the like are intended to be synonymous with“weight percent,” “wt. %,” etc.

The term “about,” as used herein, modifying the quantity of aningredient in the compositions of the invention or employed in themethods of the invention refers to variation in the numerical quantitythat can occur, for example, through typical measuring and liquidhandling procedures used for making concentrates or use solutions;through inadvertent error in these procedures; through differences inthe manufacture, source, or purity of the ingredients employed to makethe compositions or carry out the methods; and the like. The term aboutalso encompasses amounts that differ due to different equilibriumconditions for a composition resulting from a particular initialmixture. Whether or not modified by the term “about,” the claims includeequivalents to the quantities. All numeric values are herein assumed tobe modified by the term “about,” whether or not explicitly indicated.The term “about” generally refers to a range of numbers that one ofskill in the art would consider equivalent to the recited value (i.e.,having the same function or result). In many instances, the terms“about” may include numbers that are rounded to the nearest significantfigure.

The term “alkyl” or “alkyl groups,” as used herein, refers to saturatedhydrocarbons having one or more carbon atoms, including straight-chainalkyl groups (e.g., methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl,octyl, nonyl, decyl, etc.), cyclic alkyl groups (or “cycloalkyl” or“alicyclic” or “carbocyclic” groups) (e.g., cyclopropyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, etc.), branched-chain alkyl groups(e.g., isopropyl, tert-butyl, sec-butyl, isobutyl, etc.), andalkyl-substituted alkyl groups (e.g., alkyl-substituted cycloalkylgroups and cycloalkyl-substituted alkyl groups).

Unless otherwise specified, the term “alkyl” includes both“unsubstituted alkyls” and “substituted alkyls.” As used herein, theterm “substituted alkyls” refers to alkyl groups having substituentsreplacing one or more hydrogens on one or more carbons of thehydrocarbon backbone. Such substituents may include, for example,alkenyl, alkynyl, halogeno, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy,alkoxycarbonyloxy, aryloxy, aryloxycarbonyloxy, carboxylate,alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl,alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl,phosphate, phosphonato, phosphinato, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino),acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyland ureido), imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate,sulfates, alkylsulfinyl, sulfonates, sulfamoyl, sulfonamido, nitro,trifluoromethyl, cyano, azido, heterocyclic, alkylaryl, or aromatic(including heteroaromatic) groups. In some embodiments, substitutedalkyls can include a heterocyclic group. As used herein, the term“heterocyclic group” includes closed ring structures analogous tocarbocyclic groups in which one or more of the carbon atoms in the ringis an element other than carbon, for example, nitrogen, sulfur oroxygen. Heterocyclic groups may be saturated or unsaturated. Exemplaryheterocyclic groups include, but are not limited to, aziridine, ethyleneoxide (epoxides, oxiranes), thiirane (episulfides), dioxirane,azetidine, oxetane, thietane, dioxetane, dithietane, dithiete,azolidine, pyrrolidine, pyrroline, oxolane, dihydrofuran, and furan.

The term “aromatic” as used herein, refers to a hydrocarbon withalternating double and single bonds between carbon atoms forming rings.The configuration of six carbon atoms in aromatic compounds is known asa benzene ring, after the simplest possible such hydrocarbon, benzene.Aromatic hydrocarbons can be monocyclic (MAH) or polycyclic (PAH). Inone embodiment, “aromatic” is a 6-12 membered monocylic or bicyclicsystem. Aromatics include, but are not limited to, benzyl, phenyl,naphthalenyl, fluorenyl, indenyl, azulenyl, and anthracenyl.

Differentiation of antimicrobial “-cidal” or “-static” activity, thedefinitions which describe the degree of efficacy, and the officiallaboratory protocols for measuring this efficacy are considerations forunderstanding the relevance of antimicrobial agents and compositions.Antimicrobial compositions can affect two kinds of microbial celldamage. The first is a lethal, irreversible action resulting in completemicrobial cell destruction or incapacitation. The second type of celldamage is reversible, such that if the organism is rendered free of theagent, it can again multiply. The former is termed bactericidal and thelater, bacteriostatic. A sanitizer and a disinfectant are, bydefinition, agents which provide antibacterial or bactericidal activity.In contrast, a preservative is generally described as an inhibitor orbacteriostatic composition.

For the purpose of this patent application, successful reduction ofmicroorganisms is achieved when the populations of microorganisms arereduced by about 50%, by significantly more than is achieved by a washwith water, or at least about 0.3-1 log.sub.10: Larger reductions inmicrobial population provide greater levels of protection. In thisapplication, such a population reduction is the minimum acceptable forthe processes. Any increased reduction in population of microorganismsis an added benefit that provides higher levels of protection.

The term “disinfectant,” as used herein, refers to an agent that killsall vegetative cells including most recognized pathogenicmicroorganisms, using the procedure described in A.O.A.C. Use DilutionMethods, Official Methods of Analysis of the Association of OfficialAnalytical Chemists, paragraph 955.14 and applicable sections, 15.sup.thEdition, 1990 (EPA Guideline 91-2). As used herein, the term “high leveldisinfection” or “high level disinfectant” refers to a compound orcomposition that kills substantially all organisms, except high levelsof bacterial spores, and is effected with a chemical germicide clearedfor marketing as a sterilant by the Food and Drug Administration. Asused herein, the term “intermediate-level disinfection” or “intermediatelevel disinfectant” refers to a compound or composition that killsmycobacteria, most viruses, and bacteria with a chemical germicideregistered as a tuberculocide by the Environmental Protection Agency(EPA). As used herein, the term “low-level disinfection” or “low leveldisinfectant” refers to a compound or composition that kills someviruses and bacteria with a chemical germicide registered as a hospitaldisinfectant by the EPA.

The phrase “food processing surface” or, “food surface,” as used herein,refers to a surface of a tool, a machine, equipment, a structure, abuilding, or the like that is employed as part of a food processing,preparation, or storage activity. Examples of food processing surfacesinclude surfaces of food processing or preparation equipment (e.g.,slicing, canning, or transport equipment, including flumes), of foodprocessing wares (e.g., utensils, dishware, wash ware, and bar glasses),and of floors, walls, or fixtures of structures in which food processingoccurs. Food processing surfaces are found and employed in foodanti-spoilage air circulation systems, aseptic packaging sanitizing,food refrigeration and cooler cleaners and sanitizers, ware washingsanitizing, blancher cleaning and sanitizing, food packaging materials,cutting board additives, third-sink sanitizing, beverage chillers andwarmers, meat chilling or scalding waters, sanitizing gels, coolingtowers, food processing antimicrobial garment sprays, andnon-to-low-aqueous food preparation lubricants, oils, and rinseadditives.

The phrase “health care surface,” as used herein, refers to a surface ofan instrument, a device, a cart, a cage, furniture, a structure, abuilding, or the like that is employed as part of a health careactivity. Examples of health care surfaces include surfaces of medicalor dental instruments, of medical or dental devices, of electronicapparatus employed for monitoring patient health, and of floors, walls,or fixtures of structures in which health care occurs. Health caresurfaces are found in hospital, surgical, infirmity, birthing, mortuary,and clinical diagnosis rooms. These surfaces can be those typified as“hard surfaces” (such as walls, floors, bed-pans, etc.), or woven andnon-woven surfaces (such as surgical garments, draperies, bed linens,bandages, etc.), or patient-care equipment (such as respirators,diagnostic equipment, shunts, body scopes, wheel chairs, beds, etc.), orsurgical and diagnostic equipment. Health care surfaces include articlesand surfaces employed in animal health care.

The term “instrument,” as used herein, refers to the various medical ordental instruments or devices that can benefit from cleaning with areduced-odor composition according to the present invention. The phrases“medical instrument”, “dental instrument”, “medical device”, “dentaldevice”, “medical equipment”, or “dental equipment” refer toinstruments, devices, tools, appliances, apparatus, and equipment usedin medicine or dentistry. Such instruments, devices, and equipment canbe cold sterilized, soaked or washed and then heat sterilized, orotherwise benefit from cleaning in a composition of the presentinvention. These various instruments, devices and equipment include, butare not limited to: diagnostic instruments, trays, pans, holders, racks,forceps, scissors, shears, saws (e.g. bone saws and their blades),hemostats, knives, chisels, rongeurs, files, nippers, drills, drillbits, rasps, burrs, spreaders, breakers, elevators, clamps, needleholders, carriers, clips, hooks, gouges, curettes, retractors,straightener, punches, extractors, scoops, keratomes, spatulas,expressors, trocars, dilators, cages, glassware, tubing, catheters,cannulas, plugs, stents, arthoscopes and related equipment, and thelike, or combinations thereof.

The terms “agricultural” or “veterinary” objects or surfaces, as usedherein, include animal feeds, animal watering stations and enclosures,animal quarters, animal veterinarian clinics (e.g. surgical or treatmentareas), animal surgical areas, and the like.

The term “microorganisms,” as used herein, refers to any noncellular orunicellular (including colonial) organism. Microorganisms include allprokaryotes. Microorganisms include bacteria (including cyanobacteria),lichens, microfungi, protozoa, virinos, viroids, viruses, (enveloped andnon-enveloped) and some algae. As used herein, the term “microbe” issynonymous with microorganism.

The term “object”, as used herein, refers to a something material thatcan be perceived by the senses, directly and/or indirectly. Objectsinclude a surface, including a hard surface (such as glass, ceramics,metal, natural and synthetic rock, wood, and polymeric), an elastomer orplastic, woven and non-woven substrates, a food processing surface, ahealth care surface, and the like. Objects also include a food product(and its surfaces); a body or stream of water or a gas (e.g., an airstream); and surfaces and articles employed in hospitality andindustrial sectors.

The term “sanitizer,” as used herein, refers to an agent that reducesthe number of bacterial contaminants to safe levels as judged by publichealth requirements. In an embodiment, sanitizers for use in thisinvention will provide at least a 99.999% reduction (5-log orderreduction). These reductions can be evaluated using a procedure set outin Germicidal and Detergent Sanitizing Action of Disinfectants, OfficialMethods of Analysis of the Association of Official Analytical Chemists,paragraph 960.09 and applicable sections, 15^(th) Edition, 1990 (EPAGuideline 91-2). According to this reference a sanitizer should providea 99.999% reduction (5-log order reduction) within 30 seconds at roomtemperature, 25° C.+/−2° C., against several test organisms.

The term “ware,” as used herein, refers to items such as eating andcooking utensils, dishes, and other hard surfaces such as showers,sinks, toilets, bathtubs, countertops, windows, mirrors, transportationvehicles, and floors. As used herein, the term “warewashing” refers towashing, cleaning, or rinsing ware. Ware also refers to items made ofplastic. Types of plastics that can be cleaned with the compositionsaccording to the invention include but are not limited to, those thatinclude polycarbonate polymers (PC), acrilonitrile-butadiene-styrenepolymers (ABS), and polysulfone polymers (PS). Another exemplary plasticthat can be cleaned using the compositions of the invention includepolyethylene terephthalate (PET).

The recitation of numerical ranges by endpoints includes all numberssubsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3,3.80, 4, and 5).

The terms “include” and “including” when used in reference to a list ofmaterials refer to but are not limited to the materials so listed.

Compositions of the Invention

The present invention relates to antiviral compositions comprising asynergistic combination of an aromatic carboxylic acid with aromatichydroxyamide. The compositions provide rapid antiviral effectiveness,including most notably, effectiveness, against non-enveloped virusessuch as noroviruses. The compositions provide a substantial reduction innorovirus population, up to 3 logs in less than about one minute.

Accordingly, one aspect of the present invention is to provide anantiviral composition that is highly effective at inactivating ordestroying viruses harmful to human health, particularly noroviruses.

Compositions according to the present invention include a liquid,antiviral composition comprising:

-   -   (a) a virucidally effective amount of an aromatic carboxylic        acid;    -   (b) a viricidally effective amount of a carboxylic hydroxyamide;        and    -   (c) about 30% to about 99%, by weight, of a linear and/or        branched alcohol    -   (d) water;        wherein the composition has a pH of about 2.5 to about 6.8 for        topical formulations, and 1.0 to about 6.8 for a hard surface        cleaning formulation. The invention may also optionally include        a surfactant, particularly an aromatic sulfonated surfactant.        Additional functional components and excipients may also be        present.

In one embodiment the compositions comprise from about 0.05% by weightto about 5% by weight of aromatic carboxylic acid and from about 0.05%by weight to about 5% by weight of alkyl hydroxyamide.

Another aspect of the present invention is to provide a compositionhaving antiviral activity comprising a C₁-C₆ branched and/or linearalcohol, an aromatic carboxylic acid such as salicylic acid, benzoicacid salts, and derivatives thereof; and an aromatic hydroxyamide. Thearomatic carboxylic acids and aromatic hydroxyamides may be used singlyor in combination of two or more species in accordance the invention.Among them, salicylic acids are particularly preferred.

The following ingredients are present in an antiviral composition of thepresent invention.

Compositions with a C₁-C₆ Alcohol

The compositions of the present invention exhibit enhanced efficacyagainst viruses, particularly, non-enveloped viruses, when compared tothe efficacy of a C₁-C₆ alcohol. Whereas C₁₋₆ alcohols have littleefficacy against non-enveloped virus, the efficacy may be enhanced bycombining the C₁₋₆ alcohol with the synergistic combination of aromaticcarboxylic acid and aromatic hydroxyamide.

In one or more embodiments, the antiviral composition exhibits anincreased efficacy against non-enveloped viruses when compared to acomposition containing an equivalent amount of C₁₋₆ alcohol. In certainembodiments, a synergistic effect is seen. In other words, the efficacyof the antiviral composition against non-enveloped virus is greater thanthe sum of the efficacies of equivalent amounts of the individualcomponents.

Therefore, the present invention can provide a virucidally-enhancedalcoholic composition comprising a C₁-C₆ linear and/or branched alcohol,and the aromatic carboxylic acid and an aromatic hydroxyamide. Examplesof C₁-C₆ linear and branched alcohols include, but are not limited to,methanol, ethanol, propanol, isopropanol, butanol, pentanol, hexanol,and isomers and mixtures thereof. In one embodiment, the alcoholcomprises ethanol, propanol, or butanol, or isomers or mixtures thereof.In another embodiment, the alcohol comprises ethanol.

The antiviral composition comprises a C₁-C₆ linear and/or branchedalcohol of at least about 30 percent by weight. In embodiments whererapid antimicrobial efficacy is not a requirement, the amount of alcoholmay be reduced. In one embodiment, the composition comprises at leastabout 50 weight percent alcohol, in another embodiment, the compositioncomprises at least about 55 weight percent alcohol, in yet anotherembodiment, the composition comprises at least about 60 weight percentalcohol. More or less alcohol may be required in certain instances,depending particularly on other ingredients and/or the amounts thereofemployed in the composition. In certain embodiments, the antiviralcomposition comprises from about 30 weight percent to about 99 weightpercent alcohol, in other embodiments, the composition comprises fromabout 40 weight percent to about 95 weight percent of alcohol, in yetother embodiments, the composition comprises from about 50 weightpercent to about 90 weight percent of alcohol, and in still otherembodiments, the composition comprises from about 55 weight percent toabout 85 weight percent of alcohol, based upon the total weight of theantiviral composition.

Aromatic Carboxylic Acids

An antiviral agent used in the present invention includes one or morearomatic carboxylic acids having a pKa of about 2.5 or greater, andpreferably about 3 or greater in a virucidally effective amount. Toachieve the full advantage of the present invention, the aromaticcarboxylic acid has a pKa of about 3.5 or greater. Useful aromaticcarboxylic acids have a structural formula:

wherein R, independently, is selected from the group consisting ofhydroxy, C.sub.1-4-alkyl, C₁₋₄ alkoxy, amino, halo, phenyl, and benzyl;and n is 0, 1, or 2.

Specific examples of useful aromatic carboxylic acids include, but arenot limited to, salicylic acid (i.e., o-hydroxybenzoic acid, pKa ofabout 3), benzoic acid (pKa of 4-0.19), o-aminobenzoic acid (pKa of6.97), m-aminobenzoic acid (pKa of 4.78), p-amino-benzoic acid (pKa of4.92), o-bromobenzoic acid (pK of 2.84), m-bromobenzoic acid (pKa of3.86), o-chlorobenzoic acid (pKa of 2.92), m-chlorobenzoic acid (pKa of3.82), p-chlorobenzoic acid (pKa of 3.98), 2,4-dihydroxybenzoic acid(pKa of 2.94), 2,5-dihydroxybenzoic acid (pKa of 2.97),3,4-dihydroxybenzoic acid (pKa of 4.48), 3,5-dihydroxybenzoic acid (pKaof 4.04), ethylbenzoic acid (pKa of 4.35), m-hydroxybenzoic acid (pKa of4.06), p-hydroxybenzoic acid (pKa of 4.48), o-iodobenzoic acid (pKa of2.85), m-iodobenzoic acid (pKa of 3.80), methyl-o-aminobenzoic acid (pKaof 5.34), methyl-m-aminobenzoic acid (pKa of 5.10),methyl-o-aminobenzoic acid (pKa of 5.04), o-phenylbenzoic acid (pKa of3.46), isopropylbenzoic acid (pKa of 4.48), and mixtures thereof.Preferred aromatic carboxylic acids are salicylic acid, benzoic acid,m-hydroxybenzoic acid, p-hydroxybenzoic, o-aminobenzoic acid,m-aminobenzoic acid, p-aminobenzoic acid, and mixtures thereof. In oneembodiment, the antiviral composition comprises at least about 0.005weight percent to about 5 weight percent of an aromatic carboxylic acidsor combination thereof.

In a preferred embodiment the composition is free of other standardantiviral agents, such as phenols, bisguanidine, trihalocarbanilides,quaternary ammonium chlorides, and the like.

Aromatic Hydroxyamide

The invention also includes a virucidally effective amount of one ormore aromatic hydroxyamides. According to the invention, the aromatichydroxyamide and aromatic carboxylic acid act in synergistic combinationto provide effective control of non-enveloped viruses.

Aromatic hydroxyamides useful for the present invention have the generalformula:

Where

Rn is selected from the group consisting of hydroxyl, C₁₋₄ alkyl orbranched alkyl, C1-4 alkoxy, amino, halo, phenyl, and benzyl; and n is0, 1 or 2.

In one embodiment, the antiviral composition comprises at least about0.05 weight percent to about 5 weight percent of an aromatichydroxyamide or combination thereof.

In a preferred embodiment the composition is free of other standardantiviral agents, such as phenols, bisguanidine, trihalocarbanilides,quaternary ammonium chlorides, and the like.

Carrier

The carrier in the present composition comprises water and/or polyol. Itshould be appreciated that the water may be provided as deionized wateror as softened water. The water provided as part of the concentrate canbe relatively free of hardness. It is expected that the water can bedeionized to remove a portion of the dissolved solids. That is, theconcentrate can be formulated with water that includes dissolved solids,and can be formulated with water that can be characterized as hardwater.

Anionic Sulfonated Surfactant

In some embodiments the composition can include an anionic sulfonatedsurfactant. The surfactant can be included in a composition in an amountof 0% to about 5%, and typically 0.01% to about 3%, by weight, of thecomposition. More typically, if present at all, the composition containsabout 0.05% to about 2%, by weight of the sulfonated surfactant. Theoptional surfactant is stable at the pH of the composition and iscompatible with the other ingredients present in the composition.

The compositions, therefore, can contain an anionic surfactant having ahydrophobic moiety, such as a carbon chain including about 8 to about 30carbon atoms, and particularly about 12 to about 20 carbon atoms, andfurther has a hydrophilic moiety, of sulfate or sulfonate, Often, thehydrophobic carbon chain is etherified, such as with ethylene oxide orpropylene oxide, to impart a particular physical property, such asincreased water solubility or reduced surface tension to the anionicsurfactant.

Suitable anionic surfactants include, but are not limited to, compoundsin the classes known as alkyl sulfates, alkyl ether sulfates, alkylether sulfonates, sulfate esters of an alkylphenoxy polyoxyethyleneethanol, alpha-olefin sulfonates, beta-alkoxy alkane sulfonates,alkylaryl sulfonates, alkyl monoglyceride sulfates, alkyl monoglyceridesulfonates, sulfosuccinates, fatty acid amide polyoxyethylene sulfates,

Specific, nonlimiting classes of anionic surfactants useful in thepresent invention include, but are not limited to, a C₈-C₁₈ alkylsulfonate, a C₈-C₁₈ alkyl sulfate, a C₈-C₁₈ alkyl ether sulfate havingone or two moles of ethoxylation, a C₈-C₁₈ sulfoacetate, a C₈-C₁₈sulfosuccinate, a C₈-C₁₈ alkyl diphenyl oxide disulfonate, a C₈-C₁₈alpha-olefin sulfonate, a methyl ester sulfonate, and mixtures thereof.The C₈-C₁₈ alkyl group contains eight to eighteen carbon atoms, and canbe straight chain (e.g., lauryl) or branched (e.g., 2-ethylhexyl). Thecation of the anionic surfactant can be an alkali metal (preferablysodium or potassium), ammonium, C₁-C₄ alkylammonium (mono-, di-, tri-),or C₁-C₃ alkanolammonium (mono-, di-, tri-). Lithium and alkaline earthcations (e.g., magnesium) can be used, but are not preferred.

Specific surfactants include, but are not limited to, lauryl sulfates,octyl sulfates, 2-ethylhexyl sulfates, decyl sulfates, tridecylsulfates, cocoates, lauroyl sarcosinates, lauryl sulfosuccinates, linearC₁₀ diphenyl oxide disulfonates, lauryl sulfosuccinates, lauryl ethersulfates (1 and 2 moles ethylene oxide), myristyl sulfates, cetylsulfates, and similar surfactants.

Additional Functional Materials

The antiviral composition can include additional components or agents,such as additional functional materials. The functional materialsprovide desired properties and functionalities to the antimicrobialcomposition. For the purpose of this application, the term “functionalmaterials” include a material that when dispersed or dissolved in a useand/or concentrate solution, such as an aqueous solution, provides abeneficial property in a particular use. The antiviral composition mayoptionally contain other disinfectants, sanitizers, dyes, thickening orgelling agents, and perfumes. Some particular examples of functionalmaterials are discussed in more detail below, but it should beunderstood by those of skill in the art and others that the particularmaterials discussed are given by way of example only, and that a broadvariety of other functional materials may be used. For example, may ofthe functional material discussed below relate to materials used indisinfecting and/or cleaning applications, but it should be understoodthat other embodiments may include functional materials for use in otherapplications. Such additional functional materials or optionalcomponents typically are present, individually, from 0% to about 5%, byweight, of the composition, and, collectively, from 0% to about 20%, byweight of the composition.

Classes of optional ingredients include, but are not limited to,hydrotopes, dyes, fragrances, gelling agents, buffering agents,antioxidants, skin conditioners and protectants, chelating agents,opacifiers, vitamins, and similar classes of optional ingredients knownto persons skilled in the art. Specific classes of optional ingredientsinclude vitamins A, E, and C as vitamins; and EDTA compounds aschelating agents.

Skin Conditioners

The composition may include skin conditioners. Examples of optional skinconditioners include emollients, such as cetyl myristate, glyceryldioleate, isopropyl myrisate, lanolin, methyl laurate. PPG-9 laurate,octyl palmitate, and PPG-5 lanoate, for example. The skin conditioneralso can be a humectant, for example, glucamine and pyridoxine glycol.Occlusive skin conditioners, for example, aluminum lanolate, corn oil,methicone, coconut oil, stearyl stearate, phenyl trimethicone,trimyristin, olive oil, and synthetic wax, also can be used.Combinations of the classes of skin conditioners, in addition tomiscellaneous skin conditioners known to persons skilled in the art,alone or in combination can be used. Nonlimiting examples ofmiscellaneous skin conditioners also are disclosed in U.S. Pat. No.6,136,771, incorporated herein by reference.

Antioxidant

The composition may optionally include an antioxidant for improved skincondition through the removal of free radicals, and improved productstability. Some non-limiting examples of antioxidants include ascorbicacid and ascorbic acid derivatives, BHA, BHT, betacarotene, cysteine,erythorbic acid, hydroquinone, tocopherol and tocopherol derivatives,and the like.

If an antioxidant is included, it is preferably present in thecomposition in an amount from about 0.001 to about 2 wt. %, from about0.01 to about 1 wt. %, and from about 0.05 to about 0.5 wt. %.

Fragrance

The composition may optionally include a fragrance. Examples of possiblefragrances include natural oils or naturally derived materials, andsynthetic fragrances such as hydrocarbons, alcohols, aldehydes, ketones,esters, lactones, ethers, nitriles, and polyfunctionals. Non-limitingexamples of natural oils include the following: basil (Ocimum basilicum)oil, bay (Pimento acris) oil, bee balm (Monarda didyma) oil, bergamot(Citrus aurantium bergamia) oil, cardamom (Elettaria cardamomum) oil,cedarwood (Cedrus atlantica) oil, chamomile (Anthemis nobilis) oil,cinnamon (Cinnamomum cassia) oil, citronella (Cymbopogon nardus) oil,clary (Salvia sclarea) oil, clove (Eugenia caryophyllus) oil, cloveleaf(Eufenia caryophyllus) oil, Cyperus esculentus oil, cypress (Cupressussempervirens) oil, Eucalyptus citriodora oil, geranium maculatum oil,ginger (Zingiber officinale) oil, grapefruit (Citrus grandis) oil, hazel(Corylus avellana) nut oil, jasmine (Jasminum officinale) oil, Juniperuscommunis oil, Juniperus oxycedrus tar, Juniperus virginiana oil, kiwi(Actinidia chinensis) water, lavandin (Lavandula hybrida) oil, lavender(Lavandula angustifolia) oil, lavender (Lavandula angustifolia) water,lemon (Citrus medica limonum) oil, lemongrass (Cymbopogon schoenanthus)oil, lime (Citrus aurantifolia) oil, linden (Tilia cordata) oil, linden(Tilia cordata) water, mandarin orange (Citrus nobilis) oil, nutmeg(Myristica fragrans) oil, orange (Citrus aurantium dulcis) flower oil,orange (Citrus aurantium dulcis) oil, orange (Citrus aurantium dulcis)water, patchouli (Pogostemon cablin) oil, peppermint (Menthe piperita)oil, peppermint (Menthe peperita) water, rosemary (Rosmarinusofficinalis) oil, rose oil, rose (Rosa damascena) extract, rose (Rosamultiflora) extract, rosewood (Aniba rosaeodora) extract, sage (Salviaofficinalis) oil, sandalwood (Santalum album) oil, spearmint (Mentheviridis) oil, tea tree (Melaleuca alternifolia) oil, and ylang ylang(Cananga odorata) oil. Some non-limiting examples of synthetichydrocarbon fragrances include caryophyllene, .beta.-farnesene,limonene, .alpha.-pinene, and .beta.-pinene. Some non-limiting examplesof synthetic alcohol fragrances include Bacdanol, citronellol, linalool,phenethyl alcohol, and .alpha.-terpineol (R═H). Some non-limitingexamples of synthetic aldehyde fragrances include 2-methyl undecanal,citral, hexyl cinnamic aldehyde, isocycolcitral, lilial, and10-undecenal. Some non-limiting examples of synthetic ketone fragrancesinclude cashmeran, .alpha.-ionone, isocyclemone E, koavone, muscone, andtonalide. Some non-limiting examples of synthetic ester fragrancesinclude benzyl acetate, 4-t-butylcyclohexyl acetate (cis and trans),cedryl acetate, cyclacet, isobornyl acetate, and .alpha.-terpinylacetate (R=acetyl). Some non-limiting examples of synthetic lactonefragrances include coumarin, jasmine lactone, muskalactone, and peachaldehyde. Some non-limiting examples of synthetic ether fragrancesinclude Ambroxan, Anther, and Galaxolide. Some non-limiting examples ofsynthetic nitrile fragrances include cinnamonitrile and gernonitrile.Finally, some non-limiting examples of synthetic polyfunctionalfragrances include amyl salicylate, isoeugenol, Hedione, heliotropine,Lyral, and vanillin.

The composition may include a mixture of fragrances including a mixtureof natural and synthetic fragrances. The fragrance can be present in acomposition in an amount up to about 5 wt. %, preferably from about 0.01to about 3 wt. %, from about 0.05 to about 1 wt. %, and from about 0.1to about 0.2 wt. %.

Dye

The composition may optionally include a dye. Examples of dyes includeany water soluble or product soluble dye, any FD&C or D&C approved dye,Blue 1, FD&C Yellow 5, Resorcin Brown, Red 40, Direct Blue 86 (Miles),Basic Violet 10 (Clariant), Acid Yellow 23 (GAF), Acid Yellow 17 (SigmaChemical), Sap Green (Keyston Analine and Chemical), Metanil Yellow(Keyston Analine and Chemical), Acid Blue 9 (Hilton Davis), SandolanBlue/Acid Blue 182 (Clariant), Hisol Fast Red (Capitol Color andChemical), Fluorescein (Capitol Color and Chemical), Acid Green 25 (CibaSpecialties), and the like. The dye is preferably a water soluble dye.Also, the dye is preferably a FD&C or D&C approved dye.

The dye can be present in a use composition in an amount up to about 0.5wt. %, preferably from about 0.00001 to about 0.1 wt. %, from about0.0001 to about 0.01 wt. %, and from about 0.0001 to about 0.0005 wt. %.

pH-Adjusting Compound

The antimicrobial composition of the present invention does not relyupon a low pH or a high pH to provide a rapid reduction in microbialpopulations. Antimicrobial populations of the present invention have apH of about 5.0 to about 12.0. Within this pH range, the presentcompositions effectively reduce microbial populations, and are consumeracceptable, i.e., are mild to the skin, are phase stable, and generatecopious, stable foam. In some instances a pH adjusting compound may benecessary in a sufficient amount to provide a desired composition pH. Toachieve the full advantage of the present invention, the pH-adjustingcompound is present in an amount of about 1.5% to about 3.5%, by weight.

Examples of basic pH-adjusting compounds include, but are not limitedto, ammonia; mono-, di-, and trialkyl amines; mono-, di-, andtrialkanolamines; alkali metal and alkaline earth metal hydroxides;alkali metal phosphates; alkali sulfates; alkali metal carbonates; andmixtures thereof. However, the identity of the basic pH adjuster is notlimited, and any basic pH-adjusting compound known in the art can beused. Specific, nonlimiting examples of basic pH-adjusting compounds areammonia; sodium, potassium, and lithium hydroxide; sodium and potassiumphosphates, including hydrogen and dihydrogen phosphates; sodium andpotassium carbonate and bicarbonate; sodium and potassium sulfate andbisulfate; monoethanolamine; trimethylamine; isopropanolamine;diethanolamine; and triethanolamine.

The identity of an acidic pH-adjusting compound is not limited and anyacidic pH-adjusting compound known in the art, alone or in combination,can be used. Examples of specific acidic pH-adjusting compounds are themineral acids and polycarboxylic acids. Nonlimiting examples of mineralacids are hydrochloric acid, nitric acid, phosphoric acid, and sulfuricacid. Nonlimiting examples of polycarboxylic acids are citric acid,glycolic acid, and lactic acid.

Surfactants

The methods and compositions of the invention can also include furthersurfactants in addition to the optional anionic sulfonated surfactant.Surfactants include water soluble or water dispersible nonionic,semi-polar nonionic (supra), anionic (other than sulfonated), cationic,amphoteric, or zwitterionic surface-active agents; viscoelasticsurfactants or any combination thereof. A typical listing of the classesand species of surfactants useful herein appears in U.S. Pat. No.3,664,961 issued May 23, 1972, to Norris.

Nonionic Surfactants

Nonionic surfactants useful in the invention are generally characterizedby the presence of an organic hydrophobic group and an organichydrophilic group and are typically produced by the condensation of anorganic aliphatic, alkyl aromatic or polyoxyalkylene hydrophobiccompound with a hydrophilic alkaline oxide moiety which in commonpractice is ethylene oxide or a polyhydration product thereof,polyethylene glycol. Practically any hydrophobic compound having ahydroxyl, carboxyl, amino, or amido group with a reactive hydrogen atomcan be condensed with ethylene oxide, or its polyhydration adducts, orits mixtures with alkoxylenes such as propylene oxide to form a nonionicsurface-active agent. The length of the hydrophilic polyoxyalkylenemoiety which is condensed with any particular hydrophobic compound canbe readily adjusted to yield a water dispersible or water solublecompound having the desired degree of balance between hydrophilic andhydrophobic properties. Useful nonionic surfactants in the presentinvention include:

1. Block polyoxypropylene-polyoxyethylene polymeric compounds based uponpropylene glycol, ethylene glycol, glycerol, trimethylolpropane, andethylenediamine as the initiator reactive hydrogen compound. Examples ofpolymeric compounds made from a sequential propoxylation andethoxylation of initiator are commercially available under the tradenames Pluronic® and Tetronico manufactured by BASF Corp.

Pluronic® compounds are difunctional (two reactive hydrogens) compoundsformed by condensing ethylene oxide with a hydrophobic base formed bythe addition of propylene oxide to the two hydroxyl groups of propyleneglycol. This hydrophobic portion of the molecule weighs from 1,000 to4,000. Ethylene oxide is then added to sandwich this hydrophobe betweenhydrophilic groups, controlled by length to constitute from about 10% byweight to about 80% by weight of the final molecule.

Tetronic® compounds are tetra-functional block copolymers derived fromthe sequential addition of propylene oxide and ethylene oxide toethylenediamine. The molecular weight of the propylene oxide hydrotyperanges from 500 to 7,000; and, the hydrophile, ethylene oxide, is addedto constitute from 10% by weight to 80% by weight of the molecule.

2. Condensation products of one mole of alkyl phenol wherein the alkylchain, of straight chain or branched chain configuration, or of singleor dual alkyl constituent, contains from 8 to 18 carbon atoms with from3 to 50 moles of ethylene oxide. The alkyl group can, for example, berepresented by diisobutylene, di-amyl, polymerized propylene, iso-octyl,nonyl, and di-nonyl. These surfactants can be polyethylene,polypropylene, and polybutylene oxide condensates of alkyl phenols.Examples of commercial compounds of this chemistry are available on themarket under the trade names Igepal® manufactured by Rhone-Poulenc andTriton® manufactured by Union Carbide.

3. Condensation products of one mole of a saturated or unsaturated,straight or branched chain alcohol having from 6 to 24 carbon atoms withfrom 3 to 50 moles of ethylene oxide. The alcohol moiety can consist ofmixtures of alcohols in the above delineated carbon range or it canconsist of an alcohol having a specific number of carbon atoms withinthis range. Examples of like commercial surfactant are available underthe trade names Neodol® manufactured by Shell Chemical Co. and Alfonic®manufactured by Vista Chemical Co.

4. Condensation products of one mole of saturated or unsaturated,straight or branched chain carboxylic acid having from 8 to 18 carbonatoms with from 6 to 50 moles of ethylene oxide. The acid moiety canconsist of mixtures of acids in the above defined carbon atoms range orit can consist of an acid having a specific number of carbon atomswithin the range. Examples of commercial compounds of this chemistry areavailable on the market under the trade names Nopalcol® manufactured byHenkel Corporation and Lipopeg® manufactured by Lipo Chemicals, Inc.

In addition to ethoxylated carboxylic acids, commonly calledpolyethylene glycol esters, other alkanoic acid esters formed byreaction with glycerides, glycerin, and polyhydric (saccharide orsorbitan/sorbitol) alcohols have application in this invention. All ofthese ester moieties have one or more reactive hydrogen sites on theirmolecule which can undergo further acylation or ethylene oxide(alkoxide) addition to control the hydrophilicity of these substances.Care must be exercised when adding these fatty ester or acylatedcarbohydrates to compositions of the present invention containingamylase and/or lipase enzymes because of potential incompatibility. In apreferred embodiment the surfactant is a sorbitan ester.

Examples of Nonionic Low Foaming Surfactants Include

5. Compounds from (1) which are modified, essentially reversed, byadding ethylene oxide to ethylene glycol to provide a hydrophile ofdesignated molecular weight; and, then adding propylene oxide to obtainhydrophobic blocks on the outside (ends) of the molecule. Thehydrophobic portion of the molecule weighs from 1,000 to 3,100 with thecentral hydrophile including 10% by weight to 80% by weight of the finalmolecule. These reverse Pluronics® are manufactured by BASF Corporationunder the trade name Pluronic® R surfactants.

Likewise, the Tetronic® R surfactants are produced by BASF Corporationby the sequential addition of ethylene oxide and propylene oxide toethylenediamine. The hydrophobic portion of the molecule weighs from2,100 to 6,700 with the central hydrophile including 10% by weight to80% by weight of the final molecule.

6. Compounds from groups (1), (2), (3) and (4) which are modified by“capping” or “end blocking” the terminal hydroxy group or groups (ofmulti-functional moieties) to reduce foaming by reaction with a smallhydrophobic molecule such as propylene oxide, butylene oxide, benzylchloride; and, short chain fatty acids, alcohols or alkyl halidescontaining from 1 to 5 carbon atoms; and mixtures thereof. Also includedare reactants such as thionyl chloride which convert terminal hydroxygroups to a chloride group. Such modifications to the terminal hydroxygroup may lead to all-block, block-heteric, heteric-block or all-hetericnonionics.

Additional Examples of Effective Low Foaming Nonionics Include:

7. The alkylphenoxypolyethoxyalkanols of U.S. Pat. No. 2,903,486 issuedSep. 8, 1959 to Brown et al. and represented by the formula

in which R is an alkyl group of 8 to 9 carbon atoms, A is an alkylenechain of 3 to 4 carbon atoms, n is an integer of 7 to 16, and m is aninteger of 1 to 10.

The polyalkylene glycol condensates of U.S. Pat. No. 3,048,548 issuedAug. 7, 1962 to Martin et al. having alternating hydrophilic oxyethylenechains and hydrophobic oxypropylene chains where the weight of theterminal hydrophobic chains, the weight of the middle hydrophobic unitand the weight of the linking hydrophilic units each represent aboutone-third of the condensate.

The defoaming nonionic surfactants disclosed in U.S. Pat. No. 3,382,178issued May 7, 1968 to Lissant et al. having the general formulaZ[(OR)_(n)OH]_(z) wherein Z is alkoxylatable material, R is a radicalderived from an alkaline oxide which can be ethylene and propylene and nis an integer from, for example, 10 to 2,000 or more and z is an integerdetermined by the number of reactive oxyalkylatable groups.

The conjugated polyoxyalkylene compounds described in U.S. Pat. No.2,677,700, issued May 4, 1954 to Jackson et al. corresponding to theformula Y(C₃H₆O)_(n)(C₂H₄O)_(m) H wherein Y is the residue of organiccompound having from 1 to 6 carbon atoms and one reactive hydrogen atom,n has an average value of at least 6.4, as determined by hydroxyl numberand m has a value such that the oxyethylene portion constitutes 10% to90% by weight of the molecule.

The conjugated polyoxyalkylene compounds described in U.S. Pat. No.2,674,619, issued Apr. 6, 1954 to Lundsted et al. having the formulaY[(C₃H₆O_(n)(C₂H₄O)_(m)H]_(x) wherein Y is the residue of an organiccompound having from 2 to 6 carbon atoms and containing x reactivehydrogen atoms in which x has a value of at least 2, n has a value suchthat the molecular weight of the polyoxypropylene hydrophobic base is atleast 900 and m has value such that the oxyethylene content of themolecule is from 10% to 90% by weight. Compounds falling within thescope of the definition for Y include, for example, propylene glycol,glycerine, pentaerythritol, trimethylolpropane, ethylenediamine and thelike. The oxypropylene chains optionally, but advantageously, containsmall amounts of ethylene oxide and the oxyethylene chains alsooptionally, but advantageously, contain small amounts of propyleneoxide.

Additional conjugated polyoxyalkylene surface-active agents which areadvantageously used in the compositions of this invention correspond tothe formula: P[(C₃H₆O)_(n)(C₂H₄O)_(m)H]_(x) wherein P is the residue ofan organic compound having from 8 to 18 carbon atoms and containing xreactive hydrogen atoms in which x has a value of 1 or 2, n has a valuesuch that the molecular weight of the polyoxyethylene portion is atleast 44 and m has a value such that the oxypropylene content of themolecule is from 10% to 90% by weight. In either case the oxypropylenechains may contain optionally, but advantageously, small amounts ofethylene oxide and the oxyethylene chains may contain also optionally,but advantageously, small amounts of propylene oxide.

8. Polyhydroxy fatty acid amide surfactants suitable for use in thepresent compositions include those having the structural formulaR²CONR¹Z in which: R¹ is H, C₁-C₄ hydrocarbyl, 2-hydroxy ethyl,2-hydroxy propyl, ethoxy, propoxy group, or a mixture thereof; R is aC₅-C₃ 1 hydrocarbyl, which can be straight-chain; and Z is apolyhydroxyhydrocarbyl having a linear hydrocarbyl chain with at least 3hydroxyls directly connected to the chain, or an alkoxylated derivative(preferably ethoxylated or propoxylated) thereof. Z can be derived froma reducing sugar in a reductive amination reaction; such as a glycitylmoiety.

9. The alkyl ethoxylate condensation products of aliphatic alcohols withfrom 0 to 25 moles of ethylene oxide are suitable for use in the presentcompositions. The alkyl chain of the aliphatic alcohol can either bestraight or branched, primary or secondary, and generally contains from6 to 22 carbon atoms.

10. The ethoxylated C₆-C₁₈ fatty alcohols and C₆-C₁₈ mixed ethoxylatedand propoxylated fatty alcohols are suitable surfactants for use in thepresent compositions, particularly those that are water soluble.Suitable ethoxylated fatty alcohols include the C₁₀-C₁₈ ethoxylatedfatty alcohols with a degree of ethoxylation of from 3 to 50.

11. Suitable nonionic alkylpolysaccharide surfactants, particularly foruse in the present compositions include those disclosed in U.S. Pat. No.4,565,647, Llenado, issued Jan. 21, 1986. These surfactants include ahydrophobic group containing from 6 to 30 carbon atoms and apolysaccharide, e.g., a polyglycoside, hydrophilic group containing from1.3 to 10 saccharide units. Any reducing saccharide containing 5 or 6carbon atoms can be used, e.g., glucose, galactose and galactosylmoieties can be substituted for the glucosyl moieties. (Optionally thehydrophobic group is attached at the 2-, 3-, 4-, etc. positions thusgiving a glucose or galactose as opposed to a glucoside or galactoside).The intersaccharide bonds can be, e.g., between the one position of theadditional saccharide units and the 2-, 3-, 4-, and/or 6-positions onthe preceding saccharide units.

12. Fatty acid amide surfactants suitable for use in the presentcompositions include those having the formula: R⁶CON(R⁷)₂ in which R⁶ isan alkyl group containing from 7 to 21 carbon atoms and each R⁷ isindependently hydrogen, C₁-C₄ alkyl, C₁-C₄ hydroxyalkyl, or—(C₂H₄O)_(x)H, where x is in the range of from 1 to 3.

13. A useful class of non-ionic surfactants includes the class definedas alkoxylated amines or, most particularly, alcoholalkoxylated/aminated/alkoxylated surfactants. These non-ionicsurfactants may be at least in part represented by the general formulae:

R²⁰—(PO)_(s)N—(EO)_(t)H,

R₂0—(PO)_(s)N—(EO)_(t)H(EO)_(t)H, and

R²⁰—N(EO)_(t)H;

in which R²⁰ is an alkyl, alkenyl or other aliphatic group, or analkyl-aryl group of from 8 to 20, preferably 12 to 14 carbon atoms, EOis oxyethylene, PO is oxypropylene, s is 1 to 20, preferably 2-5, t is1-10, preferably 2-5, and u is 1-10, preferably 2-5. Other variations onthe scope of these compounds may be represented by the alternativeformula:

R²⁰—(PO)_(v)—N[(EO)_(w)H][(EO)_(z)H]

in which R²⁰ is as defined above, v is 1 to 20 (e.g., 1, 2, 3, or 4(preferably 2)), and w and z are independently 1-10, preferably 2-5.

These compounds are represented commercially by a line of products soldby Huntsman Chemicals as nonionic surfactants. A preferred chemical ofthis class includes Surfonic™. PEA 25 Amine Alkoxylate.

The treatise Nonionic Surfactants, edited by Schick, M. J., Vol. 1 ofthe Surfactant Science Series, Marcel Dekker, Inc., New York, 1983 is anexcellent reference on the wide variety of nonionic compounds generallyemployed in the practice of the present invention. A typical listing ofnonionic classes, and species of these surfactants, is given in U.S.Pat. No. 3,929,678 issued to Laughlin and Heuring on Dec. 30, 1975.Further examples are given in “Surface Active Agents and Detergents”(Vol. I and II by Schwartz, Perry and Berch).

Semi-Polar Nonionic Surfactants

The semi-polar type of nonionic surface active agents was describedsupra.

Anionic Surfactants

Also useful in the present invention are surface active substances whichare categorized as anionics because the charge on the hydrophobe isnegative; or surfactants in which the hydrophobic section of themolecule carries no charge unless the pH is elevated to neutrality orabove (e.g. carboxylic acids). Carboxylate, sulfonate, sulfate andphosphate are the polar (hydrophilic) solubilizing groups found inanionic surfactants. Of the cations (counter ions) associated with thesepolar groups, sodium, lithium and potassium impart water solubility;ammonium and substituted ammonium ions provide both water and oilsolubility; and, calcium, barium, and magnesium promote oil solubility.

As those skilled in the art understand, anionics are excellent detersivesurfactants and are therefore favored additions to heavy duty detergentcompositions. Generally, however, anionics have high foam profiles whichlimit their use alone or at high concentration levels in cleaningsystems such as CIP circuits that require strict foam control. Anionicsurface active compounds are useful to impart special chemical orphysical properties other than detergency within the composition.Anionics can be employed as gelling agents or as part of a gelling orthickening system. Anionics are excellent solubilizers and can be usedfor hydrotropic effect and cloud point control.

The majority of large volume commercial anionic surfactants can besubdivided into five major chemical classes and additional sub-groupsknown to those of skill in the art and described in “SurfactantEncyclopedia,” Cosmetics & Toiletries, Vol. 104 (2) 71-86 (1989). Thefirst class includes acylamino acids (and salts), such as acylgluamates,acyl peptides, sarcosinates (e.g. N-acyl sarcosinates), taurates (e.g.N-acyl taurates and fatty acid amides of methyl tauride), and the like.The second class includes carboxylic acids (and salts), such as alkanoicacids (and alkanoates), ester carboxylic acids (e.g. alkyl succinates),ether carboxylic acids, and the like. The third class includes sulfonicacids (and salts), such as isethionates (e.g. acyl isethionates),alkylaryl sulfonates, alkyl sulfonates, sulfosuccinates (e.g. monoestersand diesters of sulfosuccinate), and the like. The fifth class includessulfuric acid esters (and salts), such as alkyl ether sulfates, alkylsulfates, and the like.

Anionic sulfate surfactants suitable for use in the present compositionsinclude the linear and branched primary and secondary alkyl sulfates,alkyl ethoxysulfates, fatty oleyl glycerol sulfates, alkyl phenolethylene oxide ether sulfates, the C₅-C₁7 acyl-N—(C₁-C₄ alkyl) and—N—(C₁-C₂ hydroxyalkyl)glucamine sulfates, and sulfates ofalkylpolysaccharides such as the sulfates of alkylpolyglucoside (thenonionic nonsulfated compounds being described herein).

Examples of suitable synthetic, water soluble anionic detergentcompounds include the ammonium and substituted ammonium (such as mono-,di- and triethanolamine) and alkali metal (such as sodium, lithium andpotassium) salts of the alkyl mononuclear aromatic sulfonates such asthe alkyl benzene sulfonates containing from 5 to 18 carbon atoms in thealkyl group in a straight or branched chain, e.g., the salts of alkylbenzene sulfonates or of alkyl toluene, xylene, cumene and phenolsulfonates; alkyl naphthalene sulfonate, diamyl naphthalene sulfonate,and dinonyl naphthalene sulfonate and alkoxylated derivatives.

Anionic carboxylate surfactants suitable for use in the presentcompositions include the alkyl ethoxy carboxylates, the alkyl polyethoxypolycarboxylate surfactants and the soaps (e.g. alkyl carboxyls).Secondary soap surfactants (e.g. alkyl carboxyl surfactants) useful inthe present compositions include those which contain a carboxyl unitconnected to a secondary carbon. The secondary carbon can be in a ringstructure, e.g. as in p-octyl benzoic acid, or as in alkyl-substitutedcyclohexyl carboxylates. The secondary soap surfactants typicallycontain no ether linkages, no ester linkages and no hydroxyl groups.Further, they typically lack nitrogen atoms in the head-group(amphiphilic portion). Suitable secondary soap surfactants typicallycontain 11-13 total carbon atoms, although more carbons atoms (e.g., upto 16) can be present.

Other anionic detergents suitable for use in the present compositionsinclude olefin sulfonates, such as long chain alkene sulfonates, longchain hydroxyalkane sulfonates or mixtures of alkenesulfonates andhydroxyalkane-sulfonates. Also included are the alkyl sulfates, alkylpoly(ethyleneoxy)ether sulfates and aromatic poly(ethyleneoxy)sulfatessuch as the sulfates or condensation products of ethylene oxide andnonyl phenol (usually having 1 to 6 oxyethylene groups per molecule).Resin acids and hydrogenated resin acids are also suitable, such asrosin, hydrogenated rosin, and resin acids and hydrogenated resin acidspresent in or derived from tallow oil. The particular salts will besuitably selected depending upon the particular formulation and theneeds therein.

Further examples of suitable anionic surfactants are given in “SurfaceActive Agents and Detergents” (Vol. I and II by Schwartz, Perry andBerch). A variety of such surfactants are also generally disclosed inU.S. Pat. No. 3,929,678, issued Dec. 30, 1975 to Laughlin, et al. atColumn 23, line 58 through Column 29, line 23.

Cationic Surfactants

Surface active substances are classified as cationic if the charge onthe hydrotrope portion of the molecule is positive. Surfactants in whichthe hydrotrope carries no charge unless the pH is lowered close toneutrality or lower, but which are then cationic (e.g. alkyl amines),are also included in this group. In theory, cationic surfactants may besynthesized from any combination of elements containing an “onium”structure RnX+Y— and could include compounds other than nitrogen(ammonium) such as phosphorus (phosphonium) and sulfur (sulfonium). Inpractice, the cationic surfactant field is dominated by nitrogencontaining compounds, probably because synthetic routes to nitrogenouscationics are simple and straightforward and give high yields ofproduct, which can make them less expensive.

Cationic surfactants preferably include, more preferably refer to,compounds containing at least one long carbon chain hydrophobic groupand at least one positively charged nitrogen. The long carbon chaingroup may be attached directly to the nitrogen atom by simplesubstitution; or more preferably indirectly by a bridging functionalgroup or groups in so-called interrupted alkylamines and amido amines.Such functional groups can make the molecule more hydrophilic and/ormore water dispersible, more easily water solubilized by co-surfactantmixtures, and/or water soluble. For increased water solubility,additional primary, secondary or tertiary amino groups can be introducedor the amino nitrogen can be quaternized with low molecular weight alkylgroups. Further, the nitrogen can be a part of branched or straightchain moiety of varying degrees of unsaturation or of a saturated orunsaturated heterocyclic ring. In addition, cationic surfactants maycontain complex linkages having more than one cationic nitrogen atom.

The surfactant compounds classified as amine oxides, amphoterics andzwitterions are themselves typically cationic in near neutral to acidicpH solutions and can overlap surfactant classifications.Polyoxyethylated cationic surfactants generally behave like nonionicsurfactants in alkaline solution and like cationic surfactants in acidicsolution.

The simplest cationic amines, amine salts and quaternary ammoniumcompounds can be schematically drawn thus:

in which, R represents a long alkyl chain, R′, R″, and R′ may be eitherlong alkyl chains or smaller alkyl or aryl groups or hydrogen and Xrepresents an anion. The amine salts and quaternary ammonium compoundsare preferred for practical use in this invention due to their highdegree of water solubility.

The majority of large volume commercial cationic surfactants can besubdivided into four major classes and additional sub-groups known tothose of skill in the art and described in “Surfactant Encyclopedia,”Cosmetics & Toiletries, Vol. 104 (2) 86-96 (1989). The first classincludes alkylamines and their salts. The second class includes alkylimidazolines. The third class includes ethoxylated amines. The fourthclass includes quaternaries, such as alkylbenzyldimethylammonium salts,alkyl benzene salts, heterocyclic ammonium salts, tetra alkylammoniumsalts, and the like. Cationic surfactants are known to have a variety ofproperties that can be beneficial in the present compositions. Thesedesirable properties can include detergency in compositions of or belowneutral pH, antimicrobial efficacy, thickening or gelling in cooperationwith other agents, and the like.

Cationic surfactants useful in the compositions of the present inventioninclude those having the formula R¹ _(m)R² _(x)YLZ wherein each R¹ is anorganic group containing a straight or branched alkyl or alkenyl groupoptionally substituted with up to three phenyl or hydroxy groups andoptionally interrupted by up to four of the following structures:

or an isomer or mixture of these structures, and which contains from 8to 22 carbon atoms. The R¹ groups can additionally contain up to 12ethoxy groups. m is a number from 1 to 3. Preferably, no more than oneR¹ group in a molecule has 16 or more carbon atoms when m is 2, or morethan 12 carbon atoms when m is 3. Each R² is an alkyl or hydroxyalkylgroup containing from 1 to 4 carbon atoms or a benzyl group with no morethan one R² in a molecule being benzyl, and x is a number from 0 to 11,preferably from 0 to 6. The remainder of any carbon atom positions onthe Y group is filled by hydrogens.Y can be a group including, but not limited to:

or a mixture thereof.

Preferably, L is 1 or 2, with the Y groups being separated by a moietyselected from R¹ and R² analogs (preferably alkylene or alkenylene)having from 1 to 22 carbon atoms and two free carbon single bonds when Lis 2. Z is a water soluble anion, such as sulfate, methylsulfate,hydroxide, or nitrate anion, particularly preferred being sulfate ormethyl sulfate anions, in a number to give electrical neutrality of thecationic component.

Amphoteric Surfactants

Amphoteric, or ampholytic, surfactants contain both a basic and anacidic hydrophilic group and an organic hydrophobic group. These ionicentities may be any of the anionic or cationic groups described hereinfor other types of surfactants. A basic nitrogen and an acidiccarboxylate group are the typical functional groups employed as thebasic and acidic hydrophilic groups. In a few surfactants, sulfonate,sulfate, phosphonate or phosphate provide the negative charge.

Amphoteric surfactants can be broadly described as derivatives ofaliphatic secondary and tertiary amines, in which the aliphatic radicalmay be straight chain or branched and wherein one of the aliphaticsubstituents contains from 8 to 18 carbon atoms and one contains ananionic water solubilizing group, e.g., carboxy, sulfo, sulfato,phosphato, or phosphono. Amphoteric surfactants are subdivided into twomajor classes known to those of skill in the art and described in“Surfactant Encyclopedia,” Cosmetics & Toiletries, Vol. 104 (2) 69-71(1989). The first class includes acyl/dialkyl ethylenediaminederivatives (e.g. 2-alkyl hydroxyethyl imidazoline derivatives) andtheir salts. The second class includes N-alkylamino acids and theirsalts. Some amphoteric surfactants can be envisioned as fitting intoboth classes.

Amphoteric surfactants can be synthesized by methods known to those ofskill in the art. For example, 2-alkyl hydroxyethyl imidazoline issynthesized by condensation and ring closure of a long chain carboxylicacid (or a derivative) with dialkyl ethylenediamine. Commercialamphoteric surfactants are derivatized by subsequent hydrolysis andring-opening of the imidazoline ring by alkylation—for example withethyl acetate. During alkylation, one or two carboxy-alkyl groups reactto form a tertiary amine and an ether linkage with differing alkylatingagents yielding different tertiary amines. Long chain imidazolederivatives having application in the present invention generally havethe general formula:

wherein R is an acyclic hydrophobic group containing from 8 to 18 carbonatoms and M is a cation to neutralize the charge of the anion, generallysodium. Commercially prominent imidazoline-derived amphoterics that canbe employed in the present compositions include for example:Cocoamphopropionate, Cocoamphocarboxy-propionate, Cocoamphoglycinate,Cocoamphocarboxy-glycinate, Cocoamphopropyl-sulfonate, andCocoamphocarboxy-propionic acid. Preferred amphocarboxylic acids areproduced from fatty imidazolines in which the dicarboxylic acidfunctionality of the amphodicarboxylic acid is diacetic acid and/ordipropionic acid.

The carboxymethylated compounds (glycinates) described herein abovefrequently are called betaines. Betaines are a special class ofamphoteric discussed herein below in the section entitled, ZwitterionSurfactants.

Long chain N-alkylamino acids are readily prepared by reacting RNH₂, inwhich R.dbd.C₈-C₁₈ straight or branched chain alkyl, fatty amines withhalogenated carboxylic acids. Alkylation of the primary amino groups ofan amino acid leads to secondary and tertiary amines. Alkyl substituentsmay have additional amino groups that provide more than one reactivenitrogen center. Most commercial N-alkylamine acids are alkylderivatives of beta-alanine or beta-N(2-carboxyethyl)alanine Examples ofcommercial N-alkylamino acid ampholytes having application in thisinvention include alkyl beta-amino dipropionates, RN(C₂H₄COOM)₂ andRNHC₂H₄COOM. In these, R is preferably an acyclic hydrophobic groupcontaining from 8 to 18 carbon atoms, and M is a cation to neutralizethe charge of the anion.

Preferred amphoteric surfactants include those derived from coconutproducts such as coconut oil or coconut fatty acid. The more preferredof these coconut derived surfactants include as part of their structurean ethylenediamine moiety, an alkanolamide moiety, an amino acid moiety,preferably glycine, or a combination thereof; and an aliphaticsubstituent of from 8 to 18 (preferably 12) carbon atoms. Such asurfactant can also be considered an alkyl amphodicarboxylic acid.Disodium cocoampho dipropionate is one most preferred amphotericsurfactant and is commercially available under the tradename Miranol™FBS from Rhodia Inc., Cranbury, N.J. Another most preferred coconutderived amphoteric surfactant with the chemical name disodium cocoamphodiacetate is sold under the tradename Miranol C2M-SF Conc., also fromRhodia Inc., Cranbury, N.J.

A typical listing of amphoteric classes, and species of thesesurfactants, is given in U.S. Pat. No. 3,929,678 issued to Laughlin andHeuring on Dec. 30, 1975. Further examples are given in “Surface ActiveAgents and Detergents” (Vol. I and II by Schwartz, Perry and Berch).

Zwitterionic Surfactants

Zwitterionic surfactants can be thought of as a subset of the amphotericsurfactants. Zwitterionic surfactants can be broadly described asderivatives of secondary and tertiary amines, derivatives ofheterocyclic secondary and tertiary amines, or derivatives of quaternaryammonium, quaternary phosphonium or tertiary sulfonium compounds.Typically, a zwitterionic surfactant includes a positive chargedquaternary ammonium or, in some cases, a sulfonium or phosphonium ion, anegative charged carboxyl group, and an alkyl group. Zwitterionicsgenerally contain cationic and anionic groups which ionize to a nearlyequal degree in the isoelectric region of the molecule and which candevelop strong “inner-salt” attraction between positive-negative chargecenters. Examples of such zwitterionic synthetic surfactants includederivatives of aliphatic quaternary ammonium, phosphonium, and sulfoniumcompounds, in which the aliphatic radicals can be straight chain orbranched, and wherein one of the aliphatic substituents contains from 8to 18 carbon atoms and one contains an anionic water solubilizing group,e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate. Betaineand sultaine surfactants are exemplary zwitterionic surfactants for useherein.

A general formula for these compounds is:

wherein R1 contains an alkyl, alkenyl, or hydroxyalkyl radical of from 8to 18 carbon atoms having from 0 to 10 ethylene oxide moieties and from0 to 1 glyceryl moiety; Y is selected from the group consisting ofnitrogen, phosphorus, and sulfur atoms; R.sup.2 is an alkyl ormonohydroxy alkyl group containing 1 to 3 carbon atoms; x is 1 when Y isa sulfur atom and 2 when Y is a nitrogen or phosphorus atom, R³ is analkylene or hydroxy alkylene or hydroxy alkylene of from 1 to 4 carbonatoms and Z is a radical selected from the group consisting ofcarboxylate, sulfonate, sulfate, phosphonate, and phosphate groups.

Examples of zwitterionic surfactants having the structures listed aboveinclude:4-[N,N-di(2-hydroxyethyl)-N-octadecylammonio]-butane-1-car-boxylate;5-[S-3-hydroxypropyl-S-hexadecylsulfonio]-3-hydroxypentane-1-sul-fate;3-[P,P-diethyl-P-3,6,9-trioxatetracosanephosphonio]-2-hydroxypropane-1-1-phosphate;3-[N,N-dipropyl-N-3-dodecoxy-2-hydroxypropyl-ammonio]-propan-e-1-phosphonate;3-(N,N-dimethyl-N-hexadecylammonio)-propane-1-sulfonate;3-(N,N-dimethyl-N-hexadecylammonio)-2-hydroxy-propane-1-sulfonate;4-[N,N-di(2(2-hydroxyethyl)-N(2-hydroxydodecyl)ammonio]-butane-1-carboxyl-ate;3-[S-ethyl-S-(3-dodecoxy-2-hydroxypropyl)sulfonio]-propane-1-phosphat-e;3-[P,P-dimethyl-P-dodecylphosphonio]-propane-1-phosphonate; andS[N,N-di(3-hydroxypropyl)-N-hexadecylammonio]-2-hydroxy-pentane-1-sulfate.The alkyl groups contained in said detergent surfactants can be straightor branched and saturated or unsaturated.

The zwitterionic surfactant suitable for use in the present compositionsincludes a betaine of the general structure:

These surfactant betaines typically do not exhibit strong cationic oranionic characters at pH extremes nor do they show reduced watersolubility in their isoelectric range. Unlike “external” quaternaryammonium salts, betaines are compatible with anionics. Examples ofsuitable betaines include coconut acylamidopropyldimethyl betaine;hexadecyl dimethyl betaine; C₁₂₋₁₄ acylamidopropylbetaine; C₈₋₁₄acylamidohexyldiethyl betaine; 4-C₁₄₋₁₆acylmethylamidodiethylammonio-1-carboxybutane; C₁₆₋₁₈acylamidodimethylbetaine; C₁₂₋₁₆ acylamidopentanediethylbetaine; andC₁₂₋₁₆ acylmethylamidodimethylbetaine.

Sultaines useful in the present invention include those compounds havingthe formula (R(R1)₂N.sup.+R²SO³—, in which R is a C₆-C₁₈ hydrocarbylgroup, each R¹ is typically independently C₁-C₃ alkyl, e.g. methyl, andR² is a C₁-C₆ hydrocarbyl group, e.g. a C₁-C₃ alkylene orhydroxyalkylene group.

A typical listing of zwitterionic classes, and species of thesesurfactants, is given in U.S. Pat. No. 3,929,678 issued to Laughlin andHeuring on Dec. 30, 1975. Further examples are given in “Surface ActiveAgents and Detergents” (Vol. I and II by Schwartz, Perry and Berch).

Hydrotrope

The compositions of the invention may optionally include a hydrotrope,coupling agent, or solubilizer that aides in compositional stability,and aqueous formulation. Functionally speaking, the suitable couplerswhich can be employed are non-toxic and retain the active ingredients inaqueous solution throughout the temperature range and concentration towhich a concentrate or any use solution is exposed.

Any hydrotrope coupler may be used provided it does not react with theother components of the composition or negatively affect the performanceproperties of the composition. Representative classes of hydrotropiccoupling agents or solubilizers which can be employed include anionicsurfactants such as alkyl sulfates and alkane sulfonates, linear alkylbenzene or naphthalene sulfonates, secondary alkane sulfonates, alkylether sulfates or sulfonates, dialkyl sulfosuccinic acid esters, sugaresters (e.g., sorbitan esters), amine oxides (mono-, di-, or tri-alkyl)and C₈-C₁₀ alkyl glucosides. Preferred coupling agents for use in thepresent invention include n-octanesulfonate, available as NAS 8D fromEcolab Inc., n-octyl dimethylamine oxide, and the commonly availablearomatic sulfonates such as the alkyl benzene sulfonates (e.g. xylenesulfonates) or naphthalene sulfonates, aryl or alkaryl phosphate estersor their alkoxylated analogues having 1 to about 40 ethylene, propyleneor butylene oxide units or mixtures thereof. Other preferred hydrotropesinclude nonionic surfactants of C₆-C₂₄ alcohol alkoxylates (alkoxylatemeans ethoxylates, propoxylates, butoxylates, and co-or-terpolymermixtures thereof) (preferably C₆-C₁₄ alcohol alkoxylates) having 1 toabout 15 alkylene oxide groups (preferably about 4 to about 10 alkyleneoxide groups); C₆-C₂₄ alkylphenol alkoxylates (preferably C₈-C₁₀alkylphenol alkoxylates) having 1 to about 15 alkylene oxide groups(preferably about 4 to about 10 alkylene oxide groups); C₆-C₂₄alkylpolyglycosides (preferably C₆-C₂₀ alkylpolyglycosides) having 1 toabout 15 glycoside groups (preferably about 4 to about 10 glycosidegroups); C₆-C₂₄ fatty acid ester ethoxylates, propoxylates orglycerides; and C₄-C₁₂ mono or dialkanolamides.

Chelating/Sequestering Agent

The composition may include a chelating/sequestering agent such as anaminocarboxylic acid, a condensed phosphate, a phosphonate, apolyacrylate, and the like. In general, a chelating agent is a moleculecapable of coordinating (i.e., binding) the metal ions commonly found innatural water to prevent the metal ions from interfering with the actionof the other detersive ingredients of a cleaning composition. Thechelating/sequestering agent may also function as a threshold agent whenincluded in an effective amount. An iminodisuccinate (availablecommercially from Bayer as IDS™) may be used as a chelating agent.

Useful aminocarboxylic acids include, for example,N-hydroxyethylaminodiacetic acid, ethylenediaminetetraacetic acid(EDTA), hydroxyethylenediaminetetraacetic acid,diethylenetriaminepentaacetic acid,N-hydroxyethyl-ethylenediaminetriacetic acid (HEDTA),diethylenetriaminepentaacetic acid (DTPA), methylglycinediacetic acid(MGDA), glutamic acid-N,N-diacetic acid (GLDA), ethylenediaminesuccinicacid (EDDS), 2-hydroxyethyliminodiacetic acid (HEIDA), iminodisuccinicacid (IDS), 3-hydroxy-2-2′-iminodisuccinic acid (HIDS) and the like. Thecomposition may also include phosphonates such as2-phosphonobutane-1,2,4-tricarboxylic acid (PBTC),1-hydroxyethane-1,1-diphosphonic acid, CH₂C(OH)[PO(OH)₂]₂;aminotri(methylenephosphonic acid), N[CH₂PO(OH)₂]₃;aminotri(methylenephosphonate), sodium salt (ATMP), N[CH₂PO(ONa)₂]₃;2-hydroxyethyliminobis(methylenephosphonic acid),HOCH₂CH₂N[CH₂PO(OH)₂]₂; diethylenetriaminepenta(methylenephosphonicacid), (HO)₂POCH₂N[CH₂CH₂N[CH₂PO(OH)₂]₂]₂;diethylenetriaminepenta(methylenephosphonate), sodium salt (DTPMP),C₉H_((28-x))N₃ Na_(x)O₁₅P₅ (x=7);hexamethylenediamine(tetramethylenephosphonate), potassium salt,C₁₀H_((28-x))N₂K_(x)O₁₂P₄ (x=6);bis(hexamethylene)triamine(pentamethylenephosphonic acid),(HO₂)POCH₂N[(CH₂)₂N[CH₂PO(OH)₂]₂]₂; and phosphorus acid, H₃PO₃.

Thickening Agent

In some embodiments, a thickening agent may be included. Examples ofthickeners include soluble organic or inorganic thickener material.Examples of organic thickening materials include, but are not limited tocrosslinked homopolymers of acrylic acid, methacrylate polymers,cationic acrylate polymers, bentonite, Arabic, guar gum, xanthan gum,gellan gum, carboxymethyl cellulose, hydroxyethyl cellulose,hydroxymethyl cellulose, carboxyethyl cellulose, hydroxymethylcarboxypropyl cellulose, ethyl cellulose, sulfated cellulose,hydroxypropyl cellulose, methyl cellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, agar, pectin, gelatin, starch,chitosan, hydroxyethyl chitosan, polyvinyl alcohol, and polyethyleneoxide polymers with a molecular weight range between about 80,000 and10,000,000 g/mol. Examples of suitable polyethylene oxide polymers areavailable from DOW Chemical under the POLYOX Tradename. Some examples ofinorganic thickeners include clays, silicates and other well-knowninorganic thickeners. Some examples of organic thickeners includethixotropic and non-thixotropic thickeners. In some embodiments, thethickeners have some substantial proportion of water solubility topromote easy removability. Examples of useful soluble organic thickenersfor the compositions of the invention comprise carboxylated vinylpolymers such as polyacrylic acids and alkali metal salts thereof, andother similar aqueous thickeners that have some substantial proportionof water solubility. The composition of a thickening agent can bepresent in the range of approximately 0-5% by weight; more preferably0-3% by weight in cleaning solutions at use concentrations.

Film Forming Agent

The antimicrobial compositions of the invention can include a filmforming agent. The film forming agent includes an effective amount ofone or more alcohol ethoxylate compounds. Typically, one or more alcoholethoxylate compounds include an alkyl group that has 12 or fewer carbonatoms. In at least some embodiments, alcohol ethoxylate compounds mayeach independently have structure represented by Formula I:R—O—(CH₂CH₂O)_(n)—H(I) wherein R is a (C₁-C₁₂) alkyl group and n is aninteger in the range of 1 to 100. In some embodiments, R may be a(C₈-C₁₂) alkyl group, or may be a (C₈-C₁₀) alkyl group. Similarly, insome embodiments, n is an integer in the range of 10-50, or in the rangeof 15-30, or in the range of 20-25. In some embodiments, the one or morealcohol ethoxylate compounds are straight chain hydrophobes. One exampleof such an alcohol ethoxylate mixture is commercially available fromSasol under the trade name NOVEL II 1012-21. Alcohol ethoxylatesurfactants are also described in U.S. application Ser. No. 10/703,042,assigned to Ecolab, herein incorporated by reference.

The film forming agent can comprise a very broad range of weight percentof the entire composition, depending upon the desired properties. Forexample, for concentrated embodiments, the sheeting agent can comprisein the range of 0.011 to about 10% wt. more preferably 0.01 to 5% byweight of the composition.

Humectant

The composition can also optionally include one or more humectants. Ahumectant is a substance that promotes moisture retention.

Exemplary humectants that can be used include, but are not limited toglycerin, propylene glycol, sorbitol, glucose glutame, panethol,polyethylene glycol, xylitol, sucrose, alkyl polyglycosides, polybetainepolysiloxanes, and mixtures thereof. In some embodiments, thecomposition can include humectant in an amount in the range of 0.05-10%by weight

Emollients

Emollients incorporated into compositions of the present invention canserve to assist in forming a protective coating on the skin to retainmoisture. To be useful in the present invention, an emollient shouldhave a soothing action on skin, should be compatible with aqueousbuffered solutions of anionic surfactants, and should not significantlydetract from the antimicrobial action of the components utilized in thisinvention. Example emollients include, but are not limited tolanolin,mineral oil, glycerine lecithin, fatty esters, substituted fatty esters,sorbitol, xylitol, methyl gluceth-21, allantoin, isohexadecane, dioctyladipate, siloxanes, substituted siloxanes and polysiloxanes. The amountof the emollient in a composition suitable for use, should be in therange of from about 0.1% by weight to about 5% by weight.

Additional Antimicrobial Agent

The compositions may optionally include an additional antimicrobialagent or preservative. Antimicrobial agents are chemical compositionsthat can be used in the compositions to prevent microbial contaminationand deterioration of commercial products material systems, surfaces,etc. Generally, these materials fall in specific classes includingphenolics, halogen compounds, quaternary ammonium compounds, metalderivatives, amines, alkanol amines, nitro derivatives, analides,organosulfur and sulfur-nitrogen compounds and miscellaneous compounds.The given antimicrobial agent depending on chemical composition andconcentration may simply limit further proliferation of numbers of themicrobe or may destroy all or a substantial proportion of the microbialpopulation. The terms “microbes” and “microorganisms” typically referprimarily to bacteria and fungus microorganisms. In use, theantimicrobial agents are formed into the final product that when dilutedand dispensed using an aqueous stream forms an aqueous disinfectant orsanitizer composition that can be contacted with a variety of surfacesresulting in prevention of growth or the killing of a substantialproportion of the microbial population. Common antimicrobial agents thatmay be used include phenolic antimicrobials such as pentachlorophenol,orthophenylphenol; quaternary antimicrobial agents such as benzalconiumchloride, cetylpyridiniumchloride; amines and nitro containingantimicrobial compositions such ashexahydro-1,3,5-tris(2-hydroxyethyl)-s-triazine, dithiocarbamates suchas sodium dimethyldithiocarbamate, and a variety of other materialsknown in the art for their microbial properties. Antimicrobial agentsmay be encapsulated to improve stability and/or to reduce reactivitywith other materials in the detergent composition. When an antimicrobialagent or preservative is incorporated into the composition, thecomposition of an antimicrobial agent can be present in the range ofabout 0.01% by weight to 5% by weight.

Enzymes

The composition of the invention may include one or more enzymes, whichmay act by degrading or altering one or more types of soil residuesencountered thus removing the soil or making the soil more removable bya surfactant or other component of the cleaning composition. Forexample, one or more proteases can cleave complex, macromolecularprotein structures present in soil residues into simpler short chainmolecules which are, of themselves, more readily solubilized orotherwise more easily removed by solutions containing said proteases.

Suitable enzymes may include a protease, an amylase, a lipase, agluconase, a cellulase, a peroxidase, or a mixture thereof of anysuitable origin, such as vegetable, animal, bacterial, fungal or yeastorigin. Selections are influenced by factors such as pH-activity and/orstability optima, thermostability, and stability to active detergents,builders and the like. In this respect bacterial or fungal enzymes maybe preferred, such as bacterial amylases and proteases, and fungalcellulases. Preferably the enzyme may be a protease, a lipase, anamylase, or a combination thereof. Enzyme may be present in thecomposition from at least 0.01 wt %, or 0.01 to 2 wt %.

Enzyme Stabilizing System

The composition of the invention may include an enzyme stabilizingsystem. The enzyme stabilizing system can include a boric acid salt,such as an alkali metal borate or amine (e.g. an alkanolamine) borate,or an alkali metal borate, or potassium borate. The enzyme stabilizingsystem can also include other ingredients to stabilize certain enzymesor to enhance or maintain the effect of the boric acid salt.

For example, the cleaning composition of the invention can include awater soluble source of calcium and/or magnesium ions. Calcium ions aregenerally more effective than magnesium ions and are preferred herein ifonly one type of cation is being used. Cleaning and/or stabilized enzymecleaning compositions, especially liquids, may include 1 to 30, 2 to 20,or 8 to 12 millimoles of calcium ion per liter of finished composition,though variation is possible depending on factors including themultiplicity, type and levels of enzymes incorporated. Water-solublecalcium or magnesium salts may be employed, including for examplecalcium chloride, calcium hydroxide, calcium formate, calcium malate,calcium maleate, calcium hydroxide and calcium acetate; more generally,calcium sulfate or magnesium salts corresponding to the listed calciumsalts may be used. Further increased levels of calcium and/or magnesiummay of course be useful, for example for promoting the grease-cuttingaction of certain types of surfactant.

Methods of Making the Compositions

The compositions according to the invention are easily produced by anyof a number of known art techniques. Conveniently, a part of the wateris supplied to a suitable mixing vessel further provided with a stirreror agitator, and while stirring, the remaining constituents are added tothe mixing vessel, including any final amount of water needed to provideto 100% wt. of the inventive composition.

The compositions may be packaged in any suitable container particularlyflasks or bottles, including squeeze-type bottles, as well as bottlesprovided with a spray apparatus (e.g. trigger spray) which is used todispense the composition by spraying. Accordingly the compositions aredesirably provided as a ready to use product in a manually operatedspray dispensing container.

Preferably, the composition is adapted for being dispensed using atrigger spray. Alternately, preferably, the composition is adapted forbeing dispensed using a squeeze bottle through a nozzle.

Whereas the compositions of the present invention are intended to beused in the types of liquid forms described, nothing in thisspecification shall be understood as to limit the use of the compositionaccording to the invention with a further amount of water to form acleaning solution there from. In such a proposed diluted cleaningsolution, the greater the proportion of water added to form saidcleaning dilution will, the greater may be the reduction of the rateand/or efficacy of the thus formed cleaning solution.

Conversely, nothing in the specification shall be also understood tolimit the forming of a “super-concentrated” cleaning composition basedupon the composition described above. Such a super-concentratedingredient composition is essentially the same as the cleaningcompositions described above except in that they include a lesser amountof water.

Use Compositions

The compositions of the present invention include concentratecompositions and use compositions. For example, a concentratecomposition can be diluted, for example with water, to form a usecomposition. In an embodiment, a concentrate composition can be dilutedto a use solution before to application to an object. For reasons ofeconomics, the concentrate can be marketed and an end user can dilutethe concentrate with water or an aqueous diluent to a use solution.

The level of active components in the concentrate composition isdependent on the intended dilution factor and the desired antimicrobialactivity. The concentrates may be diluted with the water of dilution ata weight ratio of at least 1:2 and up to 1:256.

In other embodiments, the antiviral compositions may be combined withwater to form a use solution. The use solution can include between about0.05% to about 90% by weight of a C1 to C6 alcohol; from about 0.02% toabout 5% by weight of an aromatic carboxylic acid; from about 0.02% toabout 5% by weight of an aromatic hydroxyamide and water.

Methods Employing the Antiviral Compositions

The invention includes a method for reducing a viral population on thesurface of an object, a method for reducing the population of amicroorganism on skin, a method for treating a disease of skin, and thelike. These methods can operate on an article, surface, in a body orstream of water or a gas, or the like, by contacting the article,surface, body, or stream with a composition of the invention. Contactingcan include any of numerous methods for applying a composition of theinvention, such as spraying the compositions, immersing the article inthe compositions, foam or gel treating the article with the composition,or a combination thereof.

The compositions of the invention can be used for a variety of domesticor industrial applications, e.g., to reduce viral populations on asurface or object or in a body or stream of water. The compositions canbe applied in a variety of areas including kitchens, bathrooms,factories, hospitals, dental offices and food plants, and can be appliedto a variety of hard or soft surfaces having smooth, irregular or poroustopography. Suitable hard surfaces include, for example, architecturalsurfaces (e.g., floors, walls, windows, sinks, tables, counters andsigns); eating utensils; hard-surface medical or surgical instrumentsand devices; and hard-surface packaging. Such hard surfaces can be madefrom a variety of materials including, for example, ceramic, metal,glass, wood or hard plastic. Suitable soft surfaces include, for examplepaper; filter media; hospital and surgical linens and garments;soft-surface medical or surgical instruments and devices; andsoft-surface packaging. Such soft surfaces can be made from a variety ofmaterials including, for example, paper, fiber, woven or nonwovenfabric, soft plastics and elastomers. The compositions of the inventioncan also be applied to soft surfaces such as food and skin (e.g., ahand). The compositions can be employed as a foaming or nonfoamingenvironmental sanitizer or disinfectant.

The compositions of the invention can be included in products such assterilants, sanitizers, disinfectants, preservatives, deodorizers,antiseptics, fungicides, germicides, sporicides, virucides, detergents,bleaches, hard surface cleaners, hand soaps, waterless hand sanitizers,and pre- or post-surgical scrubs.

The compositions can also be used in veterinary products such asmammalian skin treatments or in products for sanitizing or disinfectinganimal enclosures, pens, watering stations, and veterinary treatmentareas such as inspection tables and operation rooms. The presentcompounds can be employed in an antimicrobial foot bath for livestock orpeople. The compositions of the present invention can also be employedas an antimicrobial teat dip.

In some aspects, the compositions of the present invention can beemployed for reducing the population of pathogenic microorganisms, suchas pathogens of humans, animals, and the like. The compositions exhibitactivity against pathogens including fungi, molds, bacteria, spores, andviruses, for example, S. aureus, E. coli, Streptococci, Legionella,Pseudomonas aeruginosa, mycobacteria, tuberculosis, phages, or the like,most particularly non enveloped viruses. Such pathogens can cause avariety of diseases and disorders, including mastitis or other mammalianmilking diseases, tuberculosis, and the like. The compositions of thepresent invention can reduce the population of microorganisms on skin orother external or mucosal surfaces of an animal. In addition, thepresent compositions can kill pathogenic microorganisms that spreadthrough transfer by water, air, or a surface substrate. The compositionsneed only be applied to the skin, other external or mucosal surfaces ofan animal water, air, or surface.

In some aspects, the compositions of the present invention are useful inthe cleaning or sanitizing of containers, processing facilities, orequipment in the food service or food processing industries. Thecompositions have particular value for use on food packaging materialsand equipment, and especially for cold or hot aseptic packaging.Examples of process facilities in which the compound of the inventioncan be employed include a milk line dairy, a continuous brewing system,food processing lines such as pumpable food systems and beverage lines,etc. Food service wares can be disinfected with the compound of theinvention. For example, the compounds can also be used on or in warewash machines, low temperature ware wash machines, dishware, bottlewashers, bottle chillers, warmers, third sink washers, cutting areas(e.g., water knives, slicers, cutters and saws) and egg washers.Particular treatable surfaces include packaging such as cartons,bottles, films and resins; dish ware such as glasses, plates, utensils,pots and pans; ware wash and low temperature ware wash machines; exposedfood preparation area surfaces such as sinks, counters, tables, floorsand walls; processing equipment such as tanks, vats, lines, pumps andhoses (e.g., dairy processing equipment for processing milk, cheese, icecream and other dairy products); and transportation vehicles. Containersinclude glass bottles, PVC or polyolefin film sacks, cans, polyester,PEN or PET bottles of various volumes (100 ml to 2 liter, etc.), onegallon milk containers, paper board juice or milk containers, etc.

The compositions can also be used on or in other industrial equipmentand in other industrial process streams such as heaters, cooling towers,boilers, retort waters, rinse waters, aseptic packaging wash waters, andthe like. The compounds can be used to treat microbes and odors inrecreational waters such as in pools, spas, recreational flumes andwater slides, fountains, and the like.

A filter containing the compound can reduce the population ofmicroorganisms in air and liquids. Such a filter can remove water andair-borne pathogens such as Legionella.

The compounds of the present invention can also be employed by dippingfood processing equipment into the use solution, soaking the equipmentfor a time sufficient to sanitize the equipment, and wiping or drainingexcess solution off the equipment, The compound may be further employedby spraying or wiping food processing surfaces with the use solution,keeping the surfaces wet for a time sufficient to sanitize the surfaces,and removing excess solution by wiping, draining vertically, vacuuming,etc.

The compounds of the present invention may also be used in a method ofsanitizing hard surfaces such as institutional type equipment, utensils,dishes, health care equipment or tools, and other hard surfaces.

The antiviral compounds can be applied to microbes or to soiled orcleaned surfaces using a variety of methods. These methods can operateon an object, surface, in a body or stream of water or a gas, or thelike, by contacting the object, surface, body, or stream with a compoundof the invention. Contacting can include any of numerous methods forapplying a compound, such as spraying the compound, immersing the objectin the compound, foam or gel treating the object with the compound, or acombination thereof.

A concentrate or use concentration of a compound of the presentinvention can be applied to or brought into contact with an object byany conventional method or apparatus for applying an antimicrobial orcleaning compound to an object. For example, the object can be wipedwith, sprayed with, foamed on, and/or immersed in the compound, or a usesolution made from the compound. The compound can be sprayed, foamed, orwiped onto a surface; the compound can be caused to flow over thesurface, or the surface can be dipped into the compound. Contacting canbe manual or by machine. Food processing surfaces, food products, foodprocessing or transport waters, and the like can be treated with liquid,foam, gel, aerosol, gas, wax, solid, or powdered stabilized compoundsaccording to the invention, or solutions containing these compounds.

The present invention will now be further illustrated by way of thefollowing non-limiting examples, in which parts and percentages are byweight unless otherwise indicated.

Examples Compositions According to the Invention were Prepared andTested Using a Standard Plaque Assay Protocol Per Below with MurineNorovirus (MNV-1) Plaque Assay Protocol

-   -   1. Pass cells according to Tissue Culture Protocols.    -   2. Use hemocytometer to count cells and adjust suspension to        1×10⁶ cells/ml.    -   3. “Prepare cell culture plates by adding 2 ml of the cell        suspension to each well in a six well plate. Rock plates gently        to evenly distribute cells and incubate overnight.    -   4. Perform the suspension assay. Ensure each dilution tube        contains 1.8 ml media.    -   5. Prepare 10 fold dilutions by adding 0.2 ml test        substance/virus to dilution tubes containing 1.8 ml media.    -   6. Aspirate media from cell culture plates (do not to let the        cells over dry- only do a set of six plates at a time).    -   7. Inoculate the six well plates with 500 uL of diluted virus        per well in duplicates according to dilutions indicated below:    -   8. Incubate plates for 1 hour at room temperature.    -   9. Prepare 1.5% low melting point agarose (SeaPlaque) overlay as        follows:        -   (a.) Calculate the Total Amount of overlay needed: 2 ml/well            x the # of wells        -   (b.) Re-melt 3% SeaPiaque. Add (Total Amount/2) ml to            bottle.        -   (c.) Add (Total Amount/2) ml of 2× complete MEM (see below)            to bottle.        -   (d.) Equilibrate 2×MEM to 37° C. and SeaPlaque agarose to            42° C. in a water bath. Immediately before overlaying cells,            mix both together in one bottle.    -   10. At the end of incubation, aspirate off the virus. Slowly add        2 ml overlay to each well (touch the side of the well, do not        pipet directly on the cells).    -   11. Allow the agarose to solidify (˜5-10 min).    -   12. Incubate the plates @ 35° C. for 48 hours.    -   13. Place plates in fume hood and add 2-4 ml of 10% formaldehyde        to each well. Allow the cells to fix overnight.    -   14. Aspirate off formaldehyde in fume hood.    -   15. Rinse plates and remove agarose plugs.    -   16. Add a 0.1% solution of Crystal Violet or Neutral Red to each        well and allow to stain for at least 20 minutes.    -   17. Rinse plates.    -   18. Count plaques.

2× MEM (500 ml

-   -   1. Add 9.5 g MEM powder and 2.2 g Sodium bicarbonate to 500 ml        Milli-Q water and mix well.        -   2. Then add: 56 ml FBS, 10 ml L-glutamine and 10 ml            Pen/Strep solution.

10% Formaldehyde

-   -   1:10 with Milli-Q water or PBDW

0.1% Crystal Violet or Neutral Red Solution

-   -   1. Make stock solution with 1.0 g stain into 100 ml Milli-Q or        PBDW    -   2. On the day of use, make 1:10 of stock and diluent

Compositions for Testing

Compositions according to the invention were prepared along with variouscontrols per the tables below. Note that the Controls each only have thearomatic hydroxyamine or the aromatic carboxylic acid but not both.

All numbers are listed as weight percentages

Control #1 Control #2 Example #1 Water 58.5 59 57.5 Ethanol 40 40 40Salicylic acid 1.5 0 1.5 Salicylamide 0 1.0 1.0 Total 100 100 100

Control #3 Control #2 Example #2 Water 58 59 57 Ethanol 40 40 40Salicylic acid 2 0 2 Salicylamide 0 1.0 1 Total 100 100 100

Control Control Control Control Control Example Example Example Example#4 #2 #5 #6 #7 #3 #4 4B 4B-1 Water 59 59 58 59.5 59.95 57.5 57.95 27.530 Ethanol 40 40 40 40 40 40 40 70 70 Salicylic acid 1.0 0 1.0 0 0 1.01.0 1.0 Salicylamide 0 1.0 1.0 0 0 1.0 1.0 1.0 Alphaolefin 0 0 0 0.50.05 0.5 0.05 0.5 Sulfonate Total 100 100 100 100 100 100 100 100 100Control 4B-1 pH was adjusted to 3.5 with phosphoric acid

Formulations Using Sulfonated Aromatic Surfactant

Control Control Control Control Control Example Example Example #4 #2 #5#8 #9 #5 #6 6B Water 59 59 58 59.95 59.5 57.95 57.5 27.5 Ethanol 40 4040 40 40 40 40 70 Salicylic acid 1.0 0 1.0 0 0 1.0 1.0 1.0 Salicylamide0 1.0 1.0 0 0 1.0 1.0 1.0 C6 0 0 0 0.05 0.5 0.05 0.5 0.5 DiphenyloxideTotal 100 100 100 100 100 100.0 100.0 100

Results

Log Reduction in MNV

population 30 sec

Contact Time

Formulation Log Reduction Control #1 1.19 Control #2 NDR Example #1>3.74

Log Reduction in MNV

population 30 sec Contact

Time

Formulation Log Reduction Control #3 2.99 Control #2 NDR Example #2>3.68

Log Reduction in MNV

population 30 sec

Contact Time

Formulation Log Reduction Control #4 NDR Control #3 NDR Control #5 1.34Control #6 NDR Control #7 NDR Example #3 >3.62 Example #4 >3.90

Log Reduction in MNV

population 30 sec

Contact Time

Formulation Log Reduction Control #4 NDR Control #2 NDR Control #5 1.34Control #8 NDR Control #9 NDR Example #5 >3.29 Example #6 3.44Poliovirus is a well known non-enveloped virus which is resistant toboth environmental and chemical inactivation as well as alcoholtolerant. The data from examples 4B and 6B demonstrates the virucidalefficacy of these compositions with poliovirus challenge.

Log Reduction Formulation Poliovirus Sabin1 Control 4B-1 ≦0.6 Example 4B4.2 Example 6B 5.3

The following examples also show utility as antimicrobial orbactericidal compositions as tested in time-kill suspension testingexposure at 30 seconds.

Log Reduction Log Reduction S. aureus E. coli Formulation ATCC 6538 ATCC11229 Example #1 >5 log >5 log Example #3 >5 log >5 log Example #6 >5log >5 log

As can be seen, all of the examples of the invention reduced the Murinenorovirus by greater than 3 logs. With only one of the aromaticcarboxylic acids or aromatic hydroxylamine either no virus reduction orin most cases less than one half of the virus reduction was observedshowing the synergism of the two together. This test was conducted withMurine norovirus, a standard surrogate for human norovirus.

Further the low alcohol content of these formulations when testedagainst MNV-1 is designed to set the alcohol at a sub-lethalconcentration as to not interfere or significantly contribute to thevirucidal activity.

These compositions can be formulated with greater amounts of ethanol,isopropyl alcohol or other suitable solvent for material solubility andremain efficacious.

These disclosed compositions are intended for leave-on application andmay be further developed with materials to increase their ability tostay on skin or tissue or hard surface. These materials are ancillary tothe active virucidal system. They may be further enhanced by skinconditioning agents, humectants, emollients, film-formers, viscositybuilding agents, chelating agents and the like for functional oraesthetic properties.

1. An antimicrobial composition having activity against non-envelopedviruses including norovirus comprising: a virucidally effective amountof an aromatic carboxylic acid and an aromatic hydroxyamide; a C₁-C₆linear and/or branched alcohol; and water.
 2. The composition of claim 1wherein said antiviral composition causes a greater than 3 log reductionin virus populations including non-enveloped viruses in less than oneminute.
 3. The composition of claim 1 further wherein said alcohol isethanol, isopropanol or n-propanol or mixtures thereof.
 4. Thecomposition of claim 1 wherein said aromatic hydroxyamide is present insaid composition in an amount of from about 0.05 weight percent to about5 weight percent of said composition.
 5. The composition of claim 1wherein said aromatic carboxylic acid is present in said composition inan amount of from about 0.05 weight percent to about 5 weight percent ofsaid composition.
 6. The composition of claim 1 wherein said compositionhas a pH of from about 1.0 to about 6.8.
 7. The composition of claim 1further comprising a sulfonated surfactant.
 8. The composition of claim1 that provides bactericidal as well as virucidal activity of >3 logs in30 seconds
 9. A method of reducing norovirus activity/concentration on asurface comprising: Contacting the surface with an antiviral compositioncomprising a virucidally effective combination of a C₁-C₆ linear and/orbranched alcohol, an aromatic carboxylic acid and an aromatichydroxyamide.
 10. The method of claim 9 wherein said surface is skin.11. The method of claim 9 wherein said surface is a hard surface.
 12. Anantiviral use solution having virucidal activity against non-envelopedviruses including norovirus where the use solution comprises from about0.05 weight percent to about 90 weight percent of a C1 to C6 linearand/or branched alcohol; from about 0.02 weight percent to about 5.0weight percent of an aromatic carboxylic acid; from about 0.02 weightpercent to about 5.0 weight percent of an aromatic hydroxyamide andwater.
 13. The solution of claim 12 wherein said aromatic carboxylicacid comprises from about 0.1 to about 3 weight percent of thecomposition.
 14. The solution of claim 12 wherein said aromatichydroxyamide comprises from about 0.1 weight percent to about 5 weightpercent of said composition.
 15. The solution of claim 12 furthercomprising a sulfonated surfactant.
 16. The solution of claim 12 whereinsaid aromatic carboxylic acid includes salicylic acid, and/or benzoicacid including derivatives or mixtures thereof.
 17. The solution ofclaim 12 wherein said aromatic carboxylic acid is salicylic acid. 18.The solution of claim 12 wherein said aromatic hydroxyamide issalicylamide.